FDA/CDC

The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.

Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.

Olivier Le Moal/Getty Images

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

The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.

Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.

Olivier Le Moal/Getty Images

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

The Food and Drug Administration has approved levoketoconazole (Recorlev, Xeris Biopharma) for the treatment of endogenous hypercortisolemia in adults with Cushing syndrome for whom surgery is not possible or was not curative.

Endogenous Cushing syndrome is a relatively rare condition characterized by chronically elevated cortisol levels, typically arising from a benign pituitary tumor. Left untreated, it can lead to reproductive problems and hirsutism in women, as well as serious complications, including diabetes, hypertension, tissue fragility, and mood disorders. Half of patients will die within 5 years if left untreated.

Olivier Le Moal/Getty Images

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

It’s a true Goldilocks debate: A week after the Centers for Disease Control and Prevention updated its COVID-19 isolation and quarantine guidelines – lowering isolation time – health care experts continued to debate the changes, with some calling them suitable, some saying they’re “reckless,” and at least one expert saying they’re “right in the middle.”

The controversy may lead to more updates. On Jan. 2, Anthony S. Fauci, MD, President Joe Biden’s chief medical adviser, said on CNN’s State of the Union that he anticipates further clarification of the guidelines soon.

Sparking the most debate: Infected people are not told to test before leaving isolation, the vaccinated and unvaccinated who are exposed are given some of the same advice, and the mask advice is not specific enough.

As issued on Dec. 27, the guidelines for the general public recommend:

• Anyone who tests positive should stay home and isolate for 5 days (instead of 10) and if the person has no symptoms or the symptoms resolve after 5 days, leaving the house is okay. A mask should be worn around others for 5 more days. In the event of a fever, the person must stay home until it resolves.
• If people are exposed to someone infected with COVID-19 and they have been boosted, finished the primary series of either the Pfizer or Moderna vaccine within the past 6 months, or finished the primary series of the Johnson & Johnson vaccine within the past 2 months, they should wear a mask around others for 10 days and, if possible, test on day 5. However, if symptoms develop, they should get a test and stay home.
• If people are exposed to someone infected with COVID-19 and they are unvaccinated or are more than 6 months out from their second dose of the Pfizer or Moderna vaccine (or more than 2 months after the J&J vaccine) and not boosted, they should quarantine for 5 days and then wear a mask for 5 more days. If quarantine is impossible, a mask should be worn for 10 days. A test on day 5 is suggested if possible. If symptoms occur, they should quarantine and test.

On social media and in interviews with this news organization, public health experts expressed an array of opinions.

A tweet from Eric Topol, MD, editor-in-chief of Medscape, posted the day after the new guidelines came out, had an empty box and this: “The data that support the new @CDCgov 5 day isolation period without a negative test.”

In a tweet on Jan. 2, Ashish K. Jha, MD, MPH, dean of the Brown University School of Public Health, said: “Hearing that CDC considering adding testing to isolation guidelines. That would be great. I’ve been arguing for a while that serial negative antigen tests provide a lot of confidence that someone is not contagious.”

Michael Mina, MD, PhD, chief science officer of eMed, a digital point-of-care platform enabling at-home diagnostic testing, tweeted: “CDC’s new guidance to drop isolation of positives to 5 days without a negative test is reckless. Some [people] stay infectious 3 days, some 12. I absolutely don’t want to sit next to someone who turned [positive] 5 days ago and hasn’t tested Neg. Test Neg to leave isolation early is just smart.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and an infectious disease specialist, disagrees. Typically, he said, an infected person sheds virus for 7 days. 

“If you are asymptomatic, the chances that you are shedding a significant amount of virus is very, very small,” he said in an interview.
 

Under debate

Testing: While many public health experts say a recommendation to test before leaving isolation is needed, CDC Director Rochelle Walensky, MD, explained testing was not recommended before leaving isolation because PCR testing can stay positive up to 12 weeks after a person is first infected with COVID-19.

Asked why there was not a recommendation for a rapid antigen test before leaving isolation, Dr. Walensky told CNN that it is not known how these tests perform at the end of infection and that the tests are not Food and Drug Administration–authorized for that purpose.

And while the guidelines suggest that those exposed – whether they are boosted, vaccinated, or not – should test on day 5 if possible, that recommendation should be stronger, some said. “At the very least recommend a test in those who can get it done,” said Dr. Topol.

However, making that recommendation is difficult when experts know how difficult it is for people to obtain tests now, William Schaffner, MD, professor of preventive medicine and an infectious disease specialist at Vanderbilt University, Nashville, Tenn., said in an interview.

“I am sure this was intensely debated,” Dr. Schaffner said of the recommendation on testing.

Vaccination status categories: Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, Baltimore, questioned the scientific basis behind treating the fully vaccinated (with two mRNA or one J&J vaccine) who are exposed ‘’as the equivalent of the unvaccinated when it comes to the quarantine requirement since the fully vaccinated are protected against what matters.”

Dr. Topol agreed: Guidelines “should be different for vaccinated versus unvaccinated.”

The recommendations for the exposed should definitely be simpler, Dr. Offit said. “I think it would be much simpler to just say, ‘If you are exposed, mask for 10 days,’ “ regardless of vaccination status.

Masks: The guidelines should also be more specific about the type of masks, Dr. Topol said. They should spell out that the masks need to be N95 or KN95, he said.

Science-driven or economy-driven? Was the guidance changed due more to concerns about the economy than to scientific information about infection and transmission? “It was,” Dr. Topol said.

Dr. Adalja sees it differently. “While it is true that this updated guidance will help the economy, it is based on a scientific foundation and should have been issued much earlier than it was.”
 

Tough decisions

The agency is walking a tightrope, Dr. Schaffner said, adding that he is in general agreement with what the CDC is trying to do. “The tightrope is between the public health ideal and trying to determine what will be acceptable,’’ he said.

The revised guidelines are more practical than before, others said. “The goal is harm reduction and many people just don’t do any isolation if they are faced with a 10-day period,” Dr. Adalja said.

Before issuing the new guidance, the CDC looked at the accumulating science and also took into account stresses on the health care system and other factors, Dr. Schaffner said. “Is it perfect?” Dr. Schaffner said of the new guideline. “No. Is it carefree? No. It’s right in the middle.”

Dr. Schaffner does think the messages about the new recommendations and how they were decided upon could have been communicated better, and in a more understandable manner. Some experts, for instance, led with the economy and the need for people to return to work and school when explaining the guidelines and then brought up the science behind the revisions.

That order should have been reversed, Dr. Schaffner said.

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

The Food and Drug Administration has approved inclisiran (Leqvio) as an adjunct to statins for further reduction of LDL cholesterol levels, the drug’s developer, Novartis, announced on Dec. 22, 2021.

The first-in-class small interfering RNA (siRNA) agent is also novel among peer drug therapies for its administration by injection initially, at 3 months, and thereafter twice per year.

Inclisiran is indicated for use atop maximally tolerated statins in adults with clinical cardiovascular disease or in patients with heterozygous familial hypercholesterolemia, the company reported.

Such patients who received inclisiran, compared with placebo, in the ORION-9, ORION-10, and ORION-11 randomized trials on which the FDA approval was based showed LDL-C reductions exceeding 50% over 1-2 years.

The drug works by “silencing” RNA involved in synthesis of PCSK9, which has a role in controlling the number of LDL cholesterol cell-surface receptors, a unique mechanism of action among available treatments for dyslipidemia.

Novartis, the company said, “has obtained global rights to develop, manufacture, and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

The Food and Drug Administration has approved inclisiran (Leqvio) as an adjunct to statins for further reduction of LDL cholesterol levels, the drug’s developer, Novartis, announced on Dec. 22, 2021.

The first-in-class small interfering RNA (siRNA) agent is also novel among peer drug therapies for its administration by injection initially, at 3 months, and thereafter twice per year.

Inclisiran is indicated for use atop maximally tolerated statins in adults with clinical cardiovascular disease or in patients with heterozygous familial hypercholesterolemia, the company reported.

Such patients who received inclisiran, compared with placebo, in the ORION-9, ORION-10, and ORION-11 randomized trials on which the FDA approval was based showed LDL-C reductions exceeding 50% over 1-2 years.

The drug works by “silencing” RNA involved in synthesis of PCSK9, which has a role in controlling the number of LDL cholesterol cell-surface receptors, a unique mechanism of action among available treatments for dyslipidemia.

Novartis, the company said, “has obtained global rights to develop, manufacture, and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

The Food and Drug Administration has approved inclisiran (Leqvio) as an adjunct to statins for further reduction of LDL cholesterol levels, the drug’s developer, Novartis, announced on Dec. 22, 2021.

The first-in-class small interfering RNA (siRNA) agent is also novel among peer drug therapies for its administration by injection initially, at 3 months, and thereafter twice per year.

Inclisiran is indicated for use atop maximally tolerated statins in adults with clinical cardiovascular disease or in patients with heterozygous familial hypercholesterolemia, the company reported.

Such patients who received inclisiran, compared with placebo, in the ORION-9, ORION-10, and ORION-11 randomized trials on which the FDA approval was based showed LDL-C reductions exceeding 50% over 1-2 years.

The drug works by “silencing” RNA involved in synthesis of PCSK9, which has a role in controlling the number of LDL cholesterol cell-surface receptors, a unique mechanism of action among available treatments for dyslipidemia.

Novartis, the company said, “has obtained global rights to develop, manufacture, and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The drumbeat of U.S. recalls continues for various lots of extended-release metformin because of contamination with unacceptably high levels of a nitrosamine that pose a cancer risk.

On Dec. 28, 2021, Viona Pharmaceuticals voluntarily recalled 33 lots of metformin hydrochloride extended-release tablets, USP 750 mg to the retail level, as a precautionary measure, because of possible contamination with N-nitrosodimethylamine (NDMA).

Metformin is used as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus. Patients who have received impacted lots of metformin are advised to continue taking their medication and contact their physician for advice regarding an alternative treatment

The product can be identified as white to off-white, capsule shaped, uncoated tablets, debossed with “Z,” “C” on one side and “20” on the other side, and come in bottles of 100 tablets, which have been distributed nationwide. The 33 batch numbers are listed in a company statement.

The affected product was manufactured by Cadila Healthcare, Ahmedabad, India, for U.S. distribution by Viona.

In its statement, Viona said: “NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables.”

This recall is being conducted “with the knowledge of the U.S. Food and Drug Administration,” it added.

Consumers with questions regarding this recall can contact the recall processor Eversana Life Science Services by phone at 1-888-304-5022, option 1; Monday-Friday, 8:00 a.m.–7:00 p.m. CT. Customers with medical-related questions who wish to report an adverse event or quality issues about the products being recalled should contact Viona Pharmaceuticals by phone at 888-304-5011, Monday-Friday, 8:30 p.m.–5:30 p.m., EST.
 

Latest in a long line of metformin recalls

This is the second time in 2021 that Viona has voluntarily recalled extended-release metformin tablets, 750 mg, because of potential contamination with NDMA. It recalled two lots in June, as reported by this news organization.

And in January 2021, Nostrum Laboratories recalled another lot of metformin extended-release 750-mg tablets, following on from a prior recall in November 2020.

These recalls follows 258 distinct U.S. lot recalls tracked by the FDA during the past 2 years because of unacceptably high NDMA levels in lots of metformin hydrochloride extended-release tablets.

The FDA has issued several statements about NDMA contamination of metformin formulations over the past 2 years, including a review of the methods used to detect NDMA and a summary of the information the agency had collected on excessive levels of NDMA in metformin.

According to the FDA’s 2020 summary, the agency has not yet determined how or why high levels of NDMA turn up so often in multiple batches of metformin hydrochloride extended-release tablets. However, published research attributed the contamination to certain methods of manufacturing metformin tablets.

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

The drumbeat of U.S. recalls continues for various lots of extended-release metformin because of contamination with unacceptably high levels of a nitrosamine that pose a cancer risk.

On Dec. 28, 2021, Viona Pharmaceuticals voluntarily recalled 33 lots of metformin hydrochloride extended-release tablets, USP 750 mg to the retail level, as a precautionary measure, because of possible contamination with N-nitrosodimethylamine (NDMA).

Metformin is used as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus. Patients who have received impacted lots of metformin are advised to continue taking their medication and contact their physician for advice regarding an alternative treatment

The product can be identified as white to off-white, capsule shaped, uncoated tablets, debossed with “Z,” “C” on one side and “20” on the other side, and come in bottles of 100 tablets, which have been distributed nationwide. The 33 batch numbers are listed in a company statement.

The affected product was manufactured by Cadila Healthcare, Ahmedabad, India, for U.S. distribution by Viona.

In its statement, Viona said: “NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables.”

This recall is being conducted “with the knowledge of the U.S. Food and Drug Administration,” it added.

Consumers with questions regarding this recall can contact the recall processor Eversana Life Science Services by phone at 1-888-304-5022, option 1; Monday-Friday, 8:00 a.m.–7:00 p.m. CT. Customers with medical-related questions who wish to report an adverse event or quality issues about the products being recalled should contact Viona Pharmaceuticals by phone at 888-304-5011, Monday-Friday, 8:30 p.m.–5:30 p.m., EST.
 

Latest in a long line of metformin recalls

This is the second time in 2021 that Viona has voluntarily recalled extended-release metformin tablets, 750 mg, because of potential contamination with NDMA. It recalled two lots in June, as reported by this news organization.

And in January 2021, Nostrum Laboratories recalled another lot of metformin extended-release 750-mg tablets, following on from a prior recall in November 2020.

These recalls follows 258 distinct U.S. lot recalls tracked by the FDA during the past 2 years because of unacceptably high NDMA levels in lots of metformin hydrochloride extended-release tablets.

The FDA has issued several statements about NDMA contamination of metformin formulations over the past 2 years, including a review of the methods used to detect NDMA and a summary of the information the agency had collected on excessive levels of NDMA in metformin.

According to the FDA’s 2020 summary, the agency has not yet determined how or why high levels of NDMA turn up so often in multiple batches of metformin hydrochloride extended-release tablets. However, published research attributed the contamination to certain methods of manufacturing metformin tablets.

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

The drumbeat of U.S. recalls continues for various lots of extended-release metformin because of contamination with unacceptably high levels of a nitrosamine that pose a cancer risk.

On Dec. 28, 2021, Viona Pharmaceuticals voluntarily recalled 33 lots of metformin hydrochloride extended-release tablets, USP 750 mg to the retail level, as a precautionary measure, because of possible contamination with N-nitrosodimethylamine (NDMA).

Metformin is used as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus. Patients who have received impacted lots of metformin are advised to continue taking their medication and contact their physician for advice regarding an alternative treatment

The product can be identified as white to off-white, capsule shaped, uncoated tablets, debossed with “Z,” “C” on one side and “20” on the other side, and come in bottles of 100 tablets, which have been distributed nationwide. The 33 batch numbers are listed in a company statement.

The affected product was manufactured by Cadila Healthcare, Ahmedabad, India, for U.S. distribution by Viona.

In its statement, Viona said: “NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables.”

This recall is being conducted “with the knowledge of the U.S. Food and Drug Administration,” it added.

Consumers with questions regarding this recall can contact the recall processor Eversana Life Science Services by phone at 1-888-304-5022, option 1; Monday-Friday, 8:00 a.m.–7:00 p.m. CT. Customers with medical-related questions who wish to report an adverse event or quality issues about the products being recalled should contact Viona Pharmaceuticals by phone at 888-304-5011, Monday-Friday, 8:30 p.m.–5:30 p.m., EST.
 

Latest in a long line of metformin recalls

This is the second time in 2021 that Viona has voluntarily recalled extended-release metformin tablets, 750 mg, because of potential contamination with NDMA. It recalled two lots in June, as reported by this news organization.

And in January 2021, Nostrum Laboratories recalled another lot of metformin extended-release 750-mg tablets, following on from a prior recall in November 2020.

These recalls follows 258 distinct U.S. lot recalls tracked by the FDA during the past 2 years because of unacceptably high NDMA levels in lots of metformin hydrochloride extended-release tablets.

The FDA has issued several statements about NDMA contamination of metformin formulations over the past 2 years, including a review of the methods used to detect NDMA and a summary of the information the agency had collected on excessive levels of NDMA in metformin.

According to the FDA’s 2020 summary, the agency has not yet determined how or why high levels of NDMA turn up so often in multiple batches of metformin hydrochloride extended-release tablets. However, published research attributed the contamination to certain methods of manufacturing metformin tablets.

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

The Food and Drug Administration has accepted a new drug application (NDA) for roflumilast, a topical phosphodiesterase type 4 (PDE4) inhibitor for treating psoriasis in adults and adolescents, according to a statement from the manufacturer.

Roflumilast cream (also known as ARQ-151) is a small molecule inhibitor of PDE4, an enzyme that increases proinflammatory mediators and decreases anti-inflammatory mediators. PDE4 is an established treatment target in dermatology: The FDA approved PDE-4 inhibitor crisaborole (Eucrisa) as a topical treatment for mild to moderate atopic dermatitis in 2016, and an oral PDE-4 inhibitor, orismilast, is being studied for the treatment of plaque psoriasis.

Topical roflumilast, if approved, would be the first topical PDE4 inhibitor for psoriasis in particular, according to the Arcutis Biotherapeutics statement. The cream is designed for use on the entire body, including the face and sensitive intertriginous areas.

The NDA is based on data from a pair of phase 3 randomized, double-blind 8-week studies known as DERMIS 1 and DERMIS 2 (Trials of PDE4 Inhibition with Roflumilast for the Management of Plaque Psoriasis” One and Two) and a long-term phase 2b open-label study.

DERMIS 1 and DERMIS 2 were identical multinational, multicenter studies designed to assess the safety and efficacy of 0.3% roflumilast cream. In the studies, roflumilast met its primary endpoint and patients treated with it demonstrated an Investigator Global Assessment (IGA) success rate of 42.4% compared with 6.1% for the vehicle control (P < .0001), and 37.5% compared with 6.9% for the vehicle control (P < .0001), in the DERMIS 1 and 2 trials, respectively, according to Arcutis.

In the phase 2b study, the treatment effect lasted for 52-64 weeks. Roflumilast was well tolerated across the three studies.

Overall, the most common adverse events reported in the studies were diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), upper respiratory tract infections (1%), and urinary tract infections (1%).

Roflumilast also showed statistically significant improvement compared to a vehicle on secondary endpoints including Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index-75 (PASI-75), reductions in itch as measured by the Worst Itch-Numerical Rating Scale (WI-NRS), and patient perceptions of symptoms based on the Psoriasis Symptoms Diary (PSD).

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2022, according to the manufacturer’s statement. An oral formulation of roflumilast was approved by the FDA in 2011, for reducing the risk of exacerbations of chronic obstructive pulmonary disease (COPD) in patients with severe COPD.

The Food and Drug Administration has accepted a new drug application (NDA) for roflumilast, a topical phosphodiesterase type 4 (PDE4) inhibitor for treating psoriasis in adults and adolescents, according to a statement from the manufacturer.

Roflumilast cream (also known as ARQ-151) is a small molecule inhibitor of PDE4, an enzyme that increases proinflammatory mediators and decreases anti-inflammatory mediators. PDE4 is an established treatment target in dermatology: The FDA approved PDE-4 inhibitor crisaborole (Eucrisa) as a topical treatment for mild to moderate atopic dermatitis in 2016, and an oral PDE-4 inhibitor, orismilast, is being studied for the treatment of plaque psoriasis.

Topical roflumilast, if approved, would be the first topical PDE4 inhibitor for psoriasis in particular, according to the Arcutis Biotherapeutics statement. The cream is designed for use on the entire body, including the face and sensitive intertriginous areas.

The NDA is based on data from a pair of phase 3 randomized, double-blind 8-week studies known as DERMIS 1 and DERMIS 2 (Trials of PDE4 Inhibition with Roflumilast for the Management of Plaque Psoriasis” One and Two) and a long-term phase 2b open-label study.

DERMIS 1 and DERMIS 2 were identical multinational, multicenter studies designed to assess the safety and efficacy of 0.3% roflumilast cream. In the studies, roflumilast met its primary endpoint and patients treated with it demonstrated an Investigator Global Assessment (IGA) success rate of 42.4% compared with 6.1% for the vehicle control (P < .0001), and 37.5% compared with 6.9% for the vehicle control (P < .0001), in the DERMIS 1 and 2 trials, respectively, according to Arcutis.

In the phase 2b study, the treatment effect lasted for 52-64 weeks. Roflumilast was well tolerated across the three studies.

Overall, the most common adverse events reported in the studies were diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), upper respiratory tract infections (1%), and urinary tract infections (1%).

Roflumilast also showed statistically significant improvement compared to a vehicle on secondary endpoints including Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index-75 (PASI-75), reductions in itch as measured by the Worst Itch-Numerical Rating Scale (WI-NRS), and patient perceptions of symptoms based on the Psoriasis Symptoms Diary (PSD).

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2022, according to the manufacturer’s statement. An oral formulation of roflumilast was approved by the FDA in 2011, for reducing the risk of exacerbations of chronic obstructive pulmonary disease (COPD) in patients with severe COPD.

The Food and Drug Administration has accepted a new drug application (NDA) for roflumilast, a topical phosphodiesterase type 4 (PDE4) inhibitor for treating psoriasis in adults and adolescents, according to a statement from the manufacturer.

Roflumilast cream (also known as ARQ-151) is a small molecule inhibitor of PDE4, an enzyme that increases proinflammatory mediators and decreases anti-inflammatory mediators. PDE4 is an established treatment target in dermatology: The FDA approved PDE-4 inhibitor crisaborole (Eucrisa) as a topical treatment for mild to moderate atopic dermatitis in 2016, and an oral PDE-4 inhibitor, orismilast, is being studied for the treatment of plaque psoriasis.

Topical roflumilast, if approved, would be the first topical PDE4 inhibitor for psoriasis in particular, according to the Arcutis Biotherapeutics statement. The cream is designed for use on the entire body, including the face and sensitive intertriginous areas.

The NDA is based on data from a pair of phase 3 randomized, double-blind 8-week studies known as DERMIS 1 and DERMIS 2 (Trials of PDE4 Inhibition with Roflumilast for the Management of Plaque Psoriasis” One and Two) and a long-term phase 2b open-label study.

DERMIS 1 and DERMIS 2 were identical multinational, multicenter studies designed to assess the safety and efficacy of 0.3% roflumilast cream. In the studies, roflumilast met its primary endpoint and patients treated with it demonstrated an Investigator Global Assessment (IGA) success rate of 42.4% compared with 6.1% for the vehicle control (P < .0001), and 37.5% compared with 6.9% for the vehicle control (P < .0001), in the DERMIS 1 and 2 trials, respectively, according to Arcutis.

In the phase 2b study, the treatment effect lasted for 52-64 weeks. Roflumilast was well tolerated across the three studies.

Overall, the most common adverse events reported in the studies were diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), upper respiratory tract infections (1%), and urinary tract infections (1%).

Roflumilast also showed statistically significant improvement compared to a vehicle on secondary endpoints including Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index-75 (PASI-75), reductions in itch as measured by the Worst Itch-Numerical Rating Scale (WI-NRS), and patient perceptions of symptoms based on the Psoriasis Symptoms Diary (PSD).

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2022, according to the manufacturer’s statement. An oral formulation of roflumilast was approved by the FDA in 2011, for reducing the risk of exacerbations of chronic obstructive pulmonary disease (COPD) in patients with severe COPD.

The Food and Drug Administration has approved tralokinumab for the treatment of moderate to severe atopic dermatitis (AD) in adults whose disease is not well controlled with topical prescription therapies or when those therapies are not advisable.

Olivier Le Moal/Getty Images

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. The drug, which has been developed by LEO Pharma, comes as a single-dose (150 mg) prefilled syringe with needle guard.

In two pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints. For example, at week 16, for the ECZTRA 1 and 2 monotherapy trials, respectively, 16% and 21% of patients treated with tralokinumab 300 mg every other week achieved clear or almost clear skin (IGA 0/1) versus 7% and 9% with placebo.

In addition, 25% and 33% of patients treated with tralokinumab 300 mg every other week achieved an improvement of 75% or more in the Eczema Area and Severity Index score (EASI-75) versus 13% and 10% with placebo. At 52 weeks, 51% and 60% of patients who responded at week 16 maintained IGA 0/1 response with tralokinumab 300 mg every other week in ECZTRA 1 and 2, respectively.

Finally, 60% and 57% of patients who responded at week 16 maintained EASI-75 response with tralokinumab 300 mg every other week.

In the drug’s third pivotal trial, ECZTRA 3, researchers evaluated the efficacy and safety of tralokinumab 300 mg in combination with topical corticosteroids (TCS) as needed in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy. At week 16, 38% of patients treated with tralokinumab 300 mg every other week plus TCS achieved clear or almost clear skin (IGA 0/1) versus 27% with placebo plus TCS. In addition, 56% of patients treated with tralokinumab 300 mg every other week plus TCS achieved an improvement of 75% or more in the EASI-75 versus 37% with placebo plus TCS. At 32 weeks, 89% and 92% of patients who responded at week 16 maintained response (IGA 0/1 and EASI-75, respectively) with tralokinumab 300 mg every other week.

A link to prescribing information can be found here. Tralokinumab is expected to be available by February 2022.

[email protected]

The Food and Drug Administration has approved tralokinumab for the treatment of moderate to severe atopic dermatitis (AD) in adults whose disease is not well controlled with topical prescription therapies or when those therapies are not advisable.

Olivier Le Moal/Getty Images

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. The drug, which has been developed by LEO Pharma, comes as a single-dose (150 mg) prefilled syringe with needle guard.

In two pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints. For example, at week 16, for the ECZTRA 1 and 2 monotherapy trials, respectively, 16% and 21% of patients treated with tralokinumab 300 mg every other week achieved clear or almost clear skin (IGA 0/1) versus 7% and 9% with placebo.

In addition, 25% and 33% of patients treated with tralokinumab 300 mg every other week achieved an improvement of 75% or more in the Eczema Area and Severity Index score (EASI-75) versus 13% and 10% with placebo. At 52 weeks, 51% and 60% of patients who responded at week 16 maintained IGA 0/1 response with tralokinumab 300 mg every other week in ECZTRA 1 and 2, respectively.

Finally, 60% and 57% of patients who responded at week 16 maintained EASI-75 response with tralokinumab 300 mg every other week.

In the drug’s third pivotal trial, ECZTRA 3, researchers evaluated the efficacy and safety of tralokinumab 300 mg in combination with topical corticosteroids (TCS) as needed in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy. At week 16, 38% of patients treated with tralokinumab 300 mg every other week plus TCS achieved clear or almost clear skin (IGA 0/1) versus 27% with placebo plus TCS. In addition, 56% of patients treated with tralokinumab 300 mg every other week plus TCS achieved an improvement of 75% or more in the EASI-75 versus 37% with placebo plus TCS. At 32 weeks, 89% and 92% of patients who responded at week 16 maintained response (IGA 0/1 and EASI-75, respectively) with tralokinumab 300 mg every other week.

A link to prescribing information can be found here. Tralokinumab is expected to be available by February 2022.

[email protected]

The Food and Drug Administration has approved tralokinumab for the treatment of moderate to severe atopic dermatitis (AD) in adults whose disease is not well controlled with topical prescription therapies or when those therapies are not advisable.

Olivier Le Moal/Getty Images

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. The drug, which has been developed by LEO Pharma, comes as a single-dose (150 mg) prefilled syringe with needle guard.

In two pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints. For example, at week 16, for the ECZTRA 1 and 2 monotherapy trials, respectively, 16% and 21% of patients treated with tralokinumab 300 mg every other week achieved clear or almost clear skin (IGA 0/1) versus 7% and 9% with placebo.

In addition, 25% and 33% of patients treated with tralokinumab 300 mg every other week achieved an improvement of 75% or more in the Eczema Area and Severity Index score (EASI-75) versus 13% and 10% with placebo. At 52 weeks, 51% and 60% of patients who responded at week 16 maintained IGA 0/1 response with tralokinumab 300 mg every other week in ECZTRA 1 and 2, respectively.

Finally, 60% and 57% of patients who responded at week 16 maintained EASI-75 response with tralokinumab 300 mg every other week.

In the drug’s third pivotal trial, ECZTRA 3, researchers evaluated the efficacy and safety of tralokinumab 300 mg in combination with topical corticosteroids (TCS) as needed in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy. At week 16, 38% of patients treated with tralokinumab 300 mg every other week plus TCS achieved clear or almost clear skin (IGA 0/1) versus 27% with placebo plus TCS. In addition, 56% of patients treated with tralokinumab 300 mg every other week plus TCS achieved an improvement of 75% or more in the EASI-75 versus 37% with placebo plus TCS. At 32 weeks, 89% and 92% of patients who responded at week 16 maintained response (IGA 0/1 and EASI-75, respectively) with tralokinumab 300 mg every other week.

A link to prescribing information can be found here. Tralokinumab is expected to be available by February 2022.

[email protected]

The Food and Drug Administration has granted emergency use authorization to Merck’s antiviral drug to treat adults with mild to moderate COVID-19 who are at risk for severe disease.

Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.

Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.

Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.

Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.

Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.

Two weapons against COVID

Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.

Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.

Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.

In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.

Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.

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

The Food and Drug Administration has granted emergency use authorization to Merck’s antiviral drug to treat adults with mild to moderate COVID-19 who are at risk for severe disease.

Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.

Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.

Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.

Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.

Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.

Two weapons against COVID

Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.

Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.

Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.

In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.

Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.

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

The Food and Drug Administration has granted emergency use authorization to Merck’s antiviral drug to treat adults with mild to moderate COVID-19 who are at risk for severe disease.

Similar to FDA authorization of another antiviral pill regimen – ritonavir plus nirmatrelvir, or Paxlovid – granted to Pfizer on Wednesday, molnupiravir (brand name Lagevrio) should be taken early in the course of COVID-19 illness.

Pfizer’s drug is authorized for anyone aged 12 and up. But Merck’s is only for adults aged 18 and older.

Merck filed an application for emergency use authorization with the FDA in October. The company included results of its phase 3 study showing the treatment could lead to a 50% reduction in COVID-19 hospitalizations. Data later showed this efficacy at closer to a 30% reduction. In November, an FDA advisory panel narrowly recommended the agency grant authorization by a 13-10 vote.

Animal studies found the drug may harm a fetus, so it is not recommended for pregnant people, the FDA says. It may be prescribed to a pregnant person only after their doctor determines the benefits outweigh the risks and the patient is told of those risks.

Women who may get pregnant should use a reliable method of birth control if being treated with molnupiravir and for 4 days after the final dose.

Two weapons against COVID

Two antiviral pills could be better than one, at least in terms of making more COVID-19 treatments available in early 2022. It is yet to be seen if the drugmakers will be able to keep up with demand, which could substantially increase with an expected surge in Omicron variant cases.

Ritonavir and molnupiravir join remdesivir (brand name Veklury) as available antivirals to treat COVID-19. Remdesivir is fully approved by the FDA but is given only through an IV to people in the hospital.

Officials point out that COVID-19 treatments in tablet form are more convenient for patients in the United States and across the globe, particularly where IV infusion services may be limited.

In March 2021, experts accurately predicted that the molnupiravir pill would be available by year’s end.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of SARS-CoV-2 because the agent does not target the virus’s spike protein.

Perhaps in part because of early promising results, the U.S. government announced in November intentions to purchase $1 billion worth of molnupiravir. That new order came on top of $1.2 billion worth of the pills the U.S. ordered in June.

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

More than a week after the rollout of the new, gender-neutral approach to the risk mitigation program for isotretinoin, frustration and glitches are still an issue, according to dermatologists, pharmacists, and patients.

When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.

At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.

The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.

With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.

While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.

While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.

The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.

So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.

According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.

One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.

Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.

And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.

Dr. Frieden and Dr. Goldberg have no relevant disclosures.

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

More than a week after the rollout of the new, gender-neutral approach to the risk mitigation program for isotretinoin, frustration and glitches are still an issue, according to dermatologists, pharmacists, and patients.

When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.

At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.

The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.

With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.

While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.

While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.

The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.

So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.

According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.

One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.

Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.

And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.

Dr. Frieden and Dr. Goldberg have no relevant disclosures.

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

More than a week after the rollout of the new, gender-neutral approach to the risk mitigation program for isotretinoin, frustration and glitches are still an issue, according to dermatologists, pharmacists, and patients.

When the new website and call center launched Dec. 13, hours-long hold times and repeated crashing of the website were reported as the norm, not the exception, triggering the American Academy of Dermatology Association (AADA) to request – and get – an emergency meeting on Dec. 16 with the U.S. Food and Drug Administration, which mandates the risk evaluation and mitigation strategy (REMS) for isotretinoin due to the teratogenicity of the acne medication.

At that meeting, ‘’the FDA and HHS [U.S. Department of Health and Human Services] acknowledged the concerns of dermatologists and the need for stakeholders to work collaboratively to find a solution,” Ilona Frieden, MD, chair of the AADA’s iPLEDGE workgroup and professor of dermatology at the University of California, San Francisco, said in an email interview. At the meeting, the AADA representatives described the severe impact on patient access to treatment that is resulting from the issues. The AADA also ‘’reiterated our call for a temporary pause to the program while stakeholders work to resolve the urgent issues with the platform,” she said.

The new approach, which is intended to make the experience more inclusive for transgender patients, reduces the previous three risk categories (females of reproductive potential, females not of reproductive potential, and males) to just two (those capable of getting pregnant and those not capable). The program requires physicians, patients, and pharmacists who prescribe, use, or dispense the drug to be registered, with requirements that include the use of two forms of an effective contraceptive and regular pregnancy tests by patients capable of becoming pregnant.

With reduced or no access during the technology glitches, access to the medicine was delayed for some patients. And dermatologists, pharmacists, and their staffs reported grueling hold times trying to reach the call center when the website had issues.

While the FDA agreed to help find a solution, it noted that the solution ‘’was to be found with dermatologists and pharmacists who are on the ground living the program every day,” Dr. Frieden said. No timeline for solving the issues was provided, so on Dec. 21, the AADA asked the FDA for a constructive dialogue among stakeholders within the next 24 hours, Dr. Frieden told this news organization.

While Dr. Frieden sees progress, ‘’we are disappointed that this situation continues to drag on for more than a week later, with more patients losing access to their needed medication each day.” While some prescribers have been able to log onto the portal and enter the information required, confirming some patients, large gaps remain, she said. Patients and pharmacists still report difficulties logging on. When that happens and they try to reach the call center, there are often hours-long hold times, dropped calls, or a message saying to call back.

The iPLEDGE administrator is Syneos Health, but a spokesperson for Syneos, Gary Gatyas, said the company does not maintain the system or the contact center.

So who does manage the call center and website? “The AADA has asked stakeholders, including Syneos Health, for clarification on who manages the call center and website but has not received a response,” Dr. Frieden said. “In the meeting [Dec. 16], representatives from the FDA made clear that the iPLEDGE sponsors are ultimately responsible for this REMS program,” Dr. Frieden said.

According to the FDA, isotretinoin manufacturers are part of the iPLEDGE program. On the iPLEDGE website, 12 isotretinoin products are listed, made by eight different companies.

One dermatologist maneuvering the new website who registered successfully as a provider told this news organization that he received a follow-up survey from United BioSource about the new website. This news organization contacted that company to confirm it runs the website but has not yet received a response.

Meanwhile, dermatologists continue to help frustrated patients cope with the new website and registration details. Neil S. Goldberg, MD, a dermatologist in Westchester County, New York, heard from two mothers who helped their teen daughters complete the forms by attesting they would use abstinence as contraception but then couldn’t figure out how to answer another question. As a result, their answers were interpreted as the patients saying they were using abstinence but didn’t commit to not having sexual contact with a partner capable of impregnating them. So Dr. Goldberg got an automated message back from the iPLEDGE program that the answers were a mismatch.

And in the comments section following a previous story on the problematic rollout, one reader offered a suggestion for reducing hold times to the call center: choose the Spanish option.

Dr. Frieden and Dr. Goldberg have no relevant disclosures.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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

SILVER SPRING, MD – The FDA issued approval for long-acting, injectable cabotegravir (CAB-LA) on Dec. 21, providing an alternative to daily oral tenofovir disoproxil fumarate-emtricitabine (TDC-FTC) for pre-exposure prophylaxis (PrEP) against HIV acquisition.

The priority review approval was based on phase 2b-3 clinical trial data submitted to the agency this past August, after the study was stopped early due to encouraging efficacy results of the first pre-planned interim end-point analysis.

“Although TDF-FTC PrEP could be almost astoundingly effective in preventing HIV acquisition across populations and risk exposures, the adherence to the daily protocols was really challenging and difficult to attain initially and to maintain for some of our most vulnerable populations,” Raphael Landovitz, MD, MDC, lead study investigator and co-director of The Center for HIV Identification, Prevention, and Treatment Services at UCLA, Los Angeles, told this news organization.

Dr. Landovitz noted that population level benefits observed with PrEP were limited to people who were highly engaged in health care and well resourced, but the same benefits were not observed in the most vulnerable, highest-risk populations. 

“The idea was, is there anything that we can do to improve ... choices for different options, some of which – like long-acting agents – would remove the obligation to adhere to daily prescribing or a post-coital and be more discreet,” he said.
 

Data demonstrated superiority versus TDF-FTC

Details of the prospective, phase 2b-3 randomized, double-blind, double-dummy, active-controlled trial among 4,566 cisgender MSM (men who have sex with men) and transgender women highlighted the superiority of CAB 600 mg intramuscularly versus placebo or active TDF-FTC (300 mg/200 mg), with CAB-LA reducing HIV infection risk by 66%. These results were published August 11 in the New England Journal of Medicine and previously reported by this news organization.

Investigators identified HIV infections in 57 participants (including 52 who acquired HIV infections after enrollment). The hazard ratio for incident HIV infection versus TDG-FTC was 0.34, P < .001. Notably, effects were consistent across prespecified subgroups and populations. 

Additionally, integrase strand-transfer inhibitor (INSTI) resistance mutations were detected in 1 of 4 of baseline HIV infection cases among CAB participants, while 2 of 39 incident infections in TDF-FTC participants occurred despite drug concentrations indicating good PrEP adherence. 
 

Adverse events, breakthrough infections, and other important considerations

Because the trial was halted early, long-term safety data were lacking, thereby prompting investigators to launch an ongoing, open-label extension. In the initial trial, injection site reactions were reported in 81.4% (1,724) of CAB participants, most beginning a median of 1 day (IQR 0-2 days) post-injection, mild to moderate in severity (60.8% pain, 23.7% tenderness), and lasting a median of 3 days (IQR 2-6 days). In comparison, injection site reactions were reported in 31.3% of TDF-FTC participants (who, incidentally, received at least one placebo injection).

Severe adverse events (grade 3 or higher) were similar between CAB and TDF-FTC groups, They consisted mostly of an increase in creatine kinase level (14.2% with CAB vs. 13.5% with TDF-FTC) and a decrease in creatinine clearance (7.0% with CAB vs. 8.3% with TDF-FTC).

Although weight gain was higher among CAB participants (1.23 kg/year vs. 0.37 kg/year, TDF-FTC participants), most of the differences were observed during the first 40 weeks and were driven by weight loss in the TDF-FDC group. Weight changes were similar (~1 kg/year) thereafter.

Importantly, study participants assigned CAB underwent an oral-tablet, 5-week lead-in phase, which might have contributed to eventual treatment failure.

In a companion piece published Nov. 1 in the Journal of Infectious Diseases, investigators noted that adherence to the oral lead-in was poor in roughly one-third of participants with incident, breakthrough infections. They wrote that the barriers to adherence with daily oral PrEP regimens coupled with the favorable CAB-LA safety profile suggested that “the oral phase before CAB-LA initiation might not be necessary or desirable.”

The question remains as to whether or not strategies entailing viral load or other RNA screening tests at follow-up clinic visits might be warranted. 

“It’s one of the biggest sort of ‘what’s next’ questions that’s come out of this study,” Dr. Landovitz said. “We’re now testing the strategy of using viral load or RNA screening at every visit to see if, in fact, we can catch these breakthrough infections earlier and potentially avoid resistance,” he added.

Until more data are available, Dr. Landovitz said that “the guidance for the clinician would be that until you have resistance testing back on someone who breaks through cabotegravir PrEP to use a protease inhibitor-based treatment regimen, at least initially.”

Institutional changes to ensure delivery of injections, tracking, and follow-up to ensure optimal use of long-acting PrEP agents are likely to challenge already overburdened health care systems and may require additional strategies for implementation (for example, pharmacy or at-home administration). Despite these factors, CAB-LA approval is welcome news to clinicians and patients alike.

“We’re constantly searching for new drugs to expand our repertoire of what we can provide patients,” Lina Rosengren-Hovee, MD, MPH, assistant professor of medicine and infectious disease specialist at UNC Health, Chapel Hill, N.C., said in an interview. Dr. Rosengren-Hovee was not involved in the study.

“For folks under 30, the sexual and gender minority, Black, and Latino, they are the ones with the highest need for PrEP, that are in a position that places them at higher risk for HIV. Being able to offer an injectable option is ... a game changer,” she said.

Dr. Rosengren-Hovee reports no relevant financial relationships. Dr. Landovitz has consulting relationships with Gilead, Janssen, Roche, and Cepheus.

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