News from the FDA/CDC

In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

[email protected]

In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

[email protected]

In 2019, the U.S. suicide rate dropped for the first time in 14 years, driven largely by a significant decline in firearm-related deaths, according to a new analysis of National Vital Statistics System data.

Since firearms are the “most common and most lethal” mechanism of suicide, the drop in deaths is “particularly encouraging,” Deborah M. Stone, ScD, MSW, MPH, and associates wrote in the Morbidity and Mortality Weekly Report.

The national suicide rate decreased from 14.2 per 100,000 population in 2018 to 13.9 per 100,000 in 2019, a statistically significant drop of 2.1% that reversed a 20-year trend that saw the rate increase by 33% since 1999, they said.

The rate for firearm use, which is involved in half of all suicides, declined from 7.0 per 100,000 to 6.8, for a significant change of 2.9%, said Dr. Stone and associates at the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control.

The only other method with a drop in suicide rate from 2018 to 2019 was suffocation – the second most common mechanism of injury – but the relative change of 2.3% was not significant, they noted.

Significant declines also occurred in several subgroups: Whites; those aged 15-24, 55-64, and 65-74 years; and those living in counties classified as large fringe metropolitan or micropolitan (urban cluster of ≥ 10,000 but less than 50,000 population), they said, based on data from the National Vital Statistics System.

“These declines, although encouraging, were not uniform, and several states experienced significant rate increases,” the investigators wrote.

The states with significant increases were Hawaii (30.3%) and Nebraska (20.1%), while declines in the suicide rate were significant in five states – Idaho, Indiana, Massachusetts, North Carolina, and Virginia, Dr. Stone and associates reported. Altogether, the rate fell in 31 states, increased in 18, and did not change in 2.

The significance of those changes varied between males and females. Declines were significant for females in Indiana, Massachusetts, and Washington, and for males in Florida, Kentucky, Massachusetts, North Carolina, and West Virginia. Minnesota was the only state with a significant increase among females, with Hawaii and Wyoming posting increases for males, they said.

As the response to the COVID-19 pandemic continues, the investigators pointed out, “prevention is more important than ever. Past research indicates that suicide rates remain stable or decline during infrastructure disruption (e.g., natural disasters), only to rise afterwards as the longer-term sequelae unfold in persons, families, and communities.”

[email protected]

Merck & Co. is withdrawing the U.S. indication for pembrolizumab (Keytruda) for metastatic small cell lung cancer (SCLC) in patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy, according to a company statement.

The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.

The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.

The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.

In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.

“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement

Dr. Baynes also championed the value of accelerated approvals.

“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.

However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.

For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.

The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.

In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.

A version of this article first appeared on Medscape.com.

Merck & Co. is withdrawing the U.S. indication for pembrolizumab (Keytruda) for metastatic small cell lung cancer (SCLC) in patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy, according to a company statement.

The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.

The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.

The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.

In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.

“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement

Dr. Baynes also championed the value of accelerated approvals.

“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.

However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.

For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.

The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.

In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.

A version of this article first appeared on Medscape.com.

Merck & Co. is withdrawing the U.S. indication for pembrolizumab (Keytruda) for metastatic small cell lung cancer (SCLC) in patients with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy, according to a company statement.

The move does not affect any of the drug’s other indications. The immunotherapy is used in the treatment of many different types of cancer.

The SCLC indication had been granted an accelerated approval by the Food and Drug Administration in 2019 based on tumor response rate and durability of response data from patient cohorts in two trials. However, the anti-PD-1 therapy failed to demonstrate statistically significant improved overall survival in a confirmatory trial, which is mandated after an accelerated approval.

The FDA is conducting “an industry-wide evaluation of indications based on accelerated approvals that have not yet met their postmarketing requirements,” said Merck.

In February of 2021, an indication for durvalumab (Imfinzi) was withdrawn by AstraZeneca in concert with the FDA after the drug failed to improve overall survival in unresectable metastatic bladder cancer in a confirmatory trial, as reported by Medscape Medical News.

“We will continue to rigorously evaluate the benefits of [pembrolizumab] in small cell lung cancer and other types of cancer, in pursuit of Merck’s mission to save and improve lives,” Roy Baynes, MD, chief medical officer, Merck Research Laboratories, said in the company statement

Dr. Baynes also championed the value of accelerated approvals.

“The accelerated pathways created by the FDA have been integral to the remarkable progress in oncology care over the past 5 years and have helped many cancer patients with advanced disease, including small cell lung cancer, access new treatments,” he said.

However, in the past, the FDA has been criticized for approving new cancer drugs based on surrogate markers such as response rates because, in many cases, subsequent studies often show that the drug fails to improve overall survival.

For example, a 2015 study found that 36 (67%) of 54 cancer drug approvals from 2008 to 2012 were made on the basis of surrogate markers – either tumor response rate or progression-free survival. Over a median follow-up period of 4.4 years, only 5 of those 36 drugs were shown in randomized studies to improve overall survival, as reported by Medscape Medical News.

The FDA says that it instituted the accelerated approval program to “allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint.” The program was started in 1992, in the midst of the HIV/AIDS epidemic.

In 2020, the nonprofit Friends of Cancer Research issued a white paper calling for reform in the accelerated approval process, which included a proposal to add risk assessment to surrogate endpoints that would factor in variables such as toxicity.

A version of this article first appeared on Medscape.com.

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

A version of this article first appeared on Medscape.com.

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

A version of this article first appeared on Medscape.com.

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

A version of this article first appeared on Medscape.com.

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



A version of this article first appeared on Medscape.com.

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



A version of this article first appeared on Medscape.com.

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration on Feb. 22 updated its October 2020 guidance for manufacturers developing COVID-19 vaccines, diagnostics, and treatments in the wake of circulating SARS-CoV-2 variants.

The United States is currently facing three main variant threats, according to the Centers for Disease Control and Prevention: B.1.1.7, which originated in the United Kingdom; B.1.351 from South Africa; and the P.1 variant, which originated in Brazil.

Acting FDA Commissioner Janet Woodcock, MD, said on a telephone press briefing call Feb. 22 that the FDA has already been communicating with individual manufacturers as they assess the variants’ effect on their products, but these guidelines are issued for the sake of transparency and to welcome scientific input.
 

Tailoring may be necessary

Dr. Woodcock emphasized that, “at this time, available data suggest the FDA-authorized vaccines are effective in protecting circulating strains of SARS-CoV-2.” However, in the event the strains start to show resistance, it may be necessary to tailor the vaccine to the variant.

In that case, effectiveness of a modified vaccine should be determined by data from clinical immunogenicity studies, which would compare a recipient’s immune response with virus variants induced by the modified vaccine against the immune response to the authorized vaccine, the guidance states.

Manufacturers should also study the vaccine in both nonvaccinated people and people fully vaccinated with the authorized vaccine, according to the guidance.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said on the call that the clinical immunogenicity data is needed to understand, for instance, whether a new vaccine strain is able to cover the new and old strain or whether it just covers the new strain. Information is also needed to understand whether the modified vaccine, when given to someone fully vaccinated, will still promote a positive response without introducing safety concerns.

Further discussions will be necessary to decide whether future modified vaccines may be authorized without the need for clinical studies.
 

Variants and testing

The FDA’s updated guidance for test developers, Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests, includes information that test performance can be influenced by the sequence of the variant, prevalence of the variant in the population, or design of the test. For example, molecular tests designed to detect multiple SARS-CoV-2 genetic targets are less susceptible to genetic variants than tests designed to detect a single genetic target.

The FDA already issued a safety alert on Jan. 8 to caution that genetic mutations to the virus in a patient sample can potentially change the performance of a diagnostic test. The FDA identified three tests that had been granted emergency-use authorization (EUA) that are known to be affected.

However, Dr. Woodcock said on the call, “at this time the impact does not appear to be significant.”
 

Updated guidance for therapeutics

The FDA has issued new guidance on the effect of variants on monoclonal antibody treatments.

“The FDA is aware that some of the monoclonal antibodies that have been authorized are less active against some of the SARS-CoV-2 variants that have emerged,” the FDA noted in its press release. “This guidance provides recommendations on efficient approaches to the generation of ... manufacturing and controls data that could potentially support an EUA for monoclonal antibody products that may be effective against emerging variants.”

While the FDA is monitoring the effects of variants, manufacturers bear a lot of the responsibility as well.

The FDA added: “With these guidances, the FDA is encouraging developers of drugs or biological products targeting SARS-CoV-2 to continuously monitor genomic databases for emerging SARS-CoV-2 variants and evaluate phenotypically any specific variants in the product target that are becoming prevalent or could potentially impact its activity.”

Dr.Woodcock added that “we urge all Americans to continue to get tested, get their vaccines when available, and follow important heath measures such as handwashing, masking, and social distancing.”

A version of this article first appeared on Medscape.com.

Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, walked through a multiagency attack plan for halting the spread of three COVID-19 variants earlier this week.

As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.

In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.

Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.

As part of that strategy, she said, the CDC strongly urges against nonessential travel.

In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.

She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.

She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.

Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.

Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.

Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.

As of Feb. 17, 56 million doses had been administered in the United States.
 

Top three threats

She updated the numbers on the three biggest variant threats.

Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.

“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.

The strain from South Africa (B.1.351) has been found in 19 cases in the United States.

The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
 

Outlook for March and April

Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.

“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”

CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.

“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.

“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.

Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.

Dr. Walensky said more data are needed before that question can be answered.

“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.

In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.

Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.

She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.

“I think many people would opt to get that one if they could get it sooner,” she said.

A version of this article first appeared on Medscape.com.

Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, walked through a multiagency attack plan for halting the spread of three COVID-19 variants earlier this week.

As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.

In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.

Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.

As part of that strategy, she said, the CDC strongly urges against nonessential travel.

In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.

She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.

She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.

Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.

Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.

Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.

As of Feb. 17, 56 million doses had been administered in the United States.
 

Top three threats

She updated the numbers on the three biggest variant threats.

Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.

“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.

The strain from South Africa (B.1.351) has been found in 19 cases in the United States.

The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
 

Outlook for March and April

Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.

“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”

CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.

“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.

“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.

Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.

Dr. Walensky said more data are needed before that question can be answered.

“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.

In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.

Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.

She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.

“I think many people would opt to get that one if they could get it sooner,” she said.

A version of this article first appeared on Medscape.com.

Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, walked through a multiagency attack plan for halting the spread of three COVID-19 variants earlier this week.

As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.

In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.

Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.

As part of that strategy, she said, the CDC strongly urges against nonessential travel.

In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.

She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.

She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.

Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.

Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.

Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.

As of Feb. 17, 56 million doses had been administered in the United States.
 

Top three threats

She updated the numbers on the three biggest variant threats.

Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.

“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.

The strain from South Africa (B.1.351) has been found in 19 cases in the United States.

The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
 

Outlook for March and April

Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.

“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”

CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.

“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.

“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.

Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.

Dr. Walensky said more data are needed before that question can be answered.

“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.

In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.

Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.

She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.

“I think many people would opt to get that one if they could get it sooner,” she said.

A version of this article first appeared on Medscape.com.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

A novel drug that offers multilineage protection from chemotherapy-induced myelosuppression has been approved by the Food and Drug Administration.

The drug, trilaciclib (Cosela, G1 Therapeutics) is administered intravenously as a 30-minute infusion within 4 hours prior to the start of chemotherapy. It is indicated specifically for use in adults with extensive-stage small-cell lung cancer (ES-SCLC) who are receiving chemotherapy.

Trilaciclib is a CDK4/6 inhibitor, and this action appears to protect normal bone marrow cells from the harmful effects of chemotherapy.

“For patients with extensive-stage small-cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” Albert Deisseroth, MD, PhD, of the FDA’s Center for Drug Evaluation and Research, said in an FDA press release.
 

First drug of its type

Trilaciclib “is the first and only therapy designed to help protect bone marrow (myeloprotection) when administered prior to treatment with chemotherapy,” according to the drug’s manufacturer.

Myelosuppression is one of the most severe adverse effects of chemotherapy, and it can be life-threatening. It can increase the risk of infection and lead to severe anemia and/or bleeding.

“These complications impact patients’ quality of life and may also result in chemotherapy dose reductions and delays,” Jeffrey Crawford, MD, of Duke Cancer Institute, Durham, N.C., said in a company press release.

“To date, approaches have included the use of growth factor agents to accelerate blood cell recovery after the bone marrow injury has occurred, along with antibiotics and transfusions as needed. By contrast, trilaciclib provides the first proactive approach to myelosuppression through a unique mechanism of action that helps protect the bone marrow from damage by chemotherapy.”
 

Approval based on randomized, placebo-controlled trials

The approval of trilaciclib is based on data from three randomized, double-blind, placebo-controlled studies, involving a total of 245 patients with ES-SCLC.

These patients were being treated with chemotherapy regimens that were based on the combination of carboplatin and etoposide (with or without the immunotherapy atezolizumab) or regimens that were based on topotecan.

Before receiving the chemotherapy, patients were randomly assigned to receive trilaciclib or placebo.

Results showed that patients who had received an infusion of trilaciclib before receiving chemotherapy had a lower chance of developing severe neutropenia compared with patients who received a placebo, the FDA noted. In addition, among the patients who did develop severe neutropenia, this had a shorter duration among patients who received trilaciclib than among those who received placebo.

The most common side effects of trilaciclib were fatigue; low levels of calcium, potassium, and phosphate in the blood; increased levels of aspartate aminotransferase; headache; and pneumonia.

The FDA noted that patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.

The approval received a priority review, based on the drug’s breakthrough therapy designation. As is common for such products, the company plans postmarketing activities that will assess the effects of trilaciclib on disease progression or survival with at least a 2-year follow up. This clinical trial is scheduled to start in 2022.

A version of this article first appeared on Medscape.com.

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

A version of this article first appeared on Medscape.com.

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

A version of this article first appeared on Medscape.com.

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

A version of this article first appeared on Medscape.com.