FDA/CDC

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

Centers for Disease Control and Prevention Director Rochelle Walensky, MD, has officially signed off on a recommendation by an independent panel of 11 experts to allow people with weakened immune function to get a third dose of certain COVID-19 vaccines.

The decision follows a unanimous vote by the CDC’s Advisory Committee on Immunization Practices (ACIP), which in turn came hours after the U.S. Food and Drug Administration updated its Emergency Use Authorization (EUA) for the Pfizer and Moderna mRNA vaccines.

About 7 million adults in the United States have moderately to severely impaired immune function because of a medical condition they live with or a medication they take to manage a health condition.

People who fall into this category are at higher risk of being hospitalized or dying if they get COVID-19. They are also more likely to transmit the infection. About 40% of vaccinated patients who are hospitalized with breakthrough cases are immunocompromised.

Recent studies have shown that between one-third and one-half of immunocompromised people who didn’t develop antibodies after two doses of a vaccine do get some level of protection after a third dose.

Even then, however, the protection immunocompromised people get from vaccines is not as robust as someone who has healthy immune function, and some panel members were concerned that a third dose might come with a false sense of security.

“My only concern with adding a third dose for the immunocompromised is the impression that our immunocompromised population [will] then be safe,” said ACIP member Helen Talbot, MD, MPH, an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn.

“I think the reality is they’ll be safer but still at incredibly high risk for severe disease and death,” she said.

In updating its EUA, the FDA stressed that, even after a third dose, people who are immunocompromised will still need to wear a mask indoors, socially distance, and avoid large crowds. In addition, family members and other close contacts should be fully vaccinated to protect these vulnerable individuals.
 

Johnson & Johnson not in the mix

The boosters will be available to children as young as 12 years of age who’ve had a Pfizer vaccine or those ages 18 and older who’ve gotten the Moderna vaccine.

For now, people who’ve had the one-dose Johnson & Johnson vaccine have not been cleared to get a second dose of any vaccine.

FDA experts acknowledged the gap but said that people who had received the Johnson & Johnson vaccine represented a small slice of vaccinated Americans, and said they couldn’t act before the FDA had updated its authorization for that vaccine, which the agency is actively exploring.

“We had to do what we’re doing based on the data we have in hand,” said Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the FDA, the division of the agency that regulates vaccines.

“We think at least there is a solution here for the very large majority of immunocompromised individuals, and we believe we will probably have a solution for the remainder in the not-too-distant future,” Dr. Marks said.

In its updated EUA, the FDA said that the third shots were intended for people who had undergone solid organ transplants or have an “equivalent level of immunocompromise.”
 

The details

Clinical experts on the CDC panel spent a good deal of time trying to suss out exactly what conditions might fall under the FDA’s umbrella for a third dose.

In a presentation to the committee, Neela Goswami, MD, PhD, an assistant professor of infectious diseases at Emory University School of Medicine and of epidemiology at the Emory Rollins School of Public Health, Atlanta, stressed that the shots are intended for patients who are moderately or severely immunocompromised, in close consultation with their doctors, but that people who should qualify would include those:

• Receiving treatment for solid tumors or blood cancers
• Taking immunosuppressing medications after a solid organ transplant
• Within 2 years of receiving CAR-T therapy or a stem cell transplant
• Who have primary immunodeficiencies – rare genetic disorders that prevent the immune system from working properly
• With advanced or untreated 
• Taking high-dose corticosteroids (more than 20 milligrams of  or its equivalent daily), alkylating agents, antimetabolites, chemotherapy, TNF blockers, or other immunomodulating or immunosuppressing biologics
• With certain chronic medical conditions, such as  or asplenia – living without a spleen
• Receiving dialysis

In discussion, CDC experts clarified that these third doses were not intended for people whose immune function had waned with age, such as elderly residents of long-term care facilities or people with chronic diseases like diabetes.

The idea is to try to get a third dose of the vaccine they’ve already had – Moderna or Pfizer – but if that’s not feasible, it’s fine for the third dose to be different from what someone has had before. The third dose should be given at least 28 days after a second dose, and, ideally, before the initiation of immunosuppressive therapy.

Participants in the meeting said that the CDC would post updated materials on its website to help guide physicians on exactly who should receive third doses.

Ultimately, however, the extra doses will be given on an honor system; no prescriptions or other kinds of clinical documentation will be required for people to get a third dose of these shots.

Tests to measure neutralizing antibodies are also not recommended before the shots are given because of differences in the types of tests used to measure these antibodies and the difficulty in interpreting them. It’s unclear right now what level of neutralizing antibodies is needed for protection.
 

‘Peace of mind’

In public testimony, Heather Braaten, a 44-year-old being treated for ovarian cancer, said she was grateful to have gotten two shots of the Pfizer vaccine last winter, in between rounds of chemotherapy, but she knew she was probably not well protected. She said she’d become obsessive over the past few months reading medical studies and trying to understand her risk.

“I have felt distraught over the situation. My prognosis is poor. I most likely have about two to three years left to live, so everything counts,” Ms. Braaten said.

She said her life ambitions were humble. She wants to visit with friends and family and not have to worry that she’ll be a breakthrough case. She wants to go grocery shopping again and “not panic and leave the store after five minutes.” She’d love to feel free to travel, she said.

“While I understand I still need to be cautious, I am hopeful for the peace of mind and greater freedom a third shot can provide,” Ms. Braaten said.
 

More boosters on the way?

In the second half of the meeting, the CDC also signaled that it was considering the use of boosters for people whose immunity might have waned in the months since they had completed their vaccine series, particularly seniors. About 75% of people hospitalized with vaccine breakthrough cases are over age 65, according to CDC data.

Those considerations are becoming more urgent as the Delta variant continues to pummel less vaccinated states and counties.

In its presentation to the ACIP, Heather Scobie, PhD, MPH, a member of the CDC’s COVID Response Team, highlighted data from Canada, Israel, Qatar, and the United Kingdom showing that, while the Pfizer vaccine was still highly effective at preventing hospitalizations and death, it’s far less likely when faced with Delta to prevent an infection that causes symptoms.

In Israel, Pfizer’s vaccine prevented symptoms an average of 41% of the time. In Qatar, which is also using the Moderna vaccine, Pfizer’s prevented symptomatic infections with Delta about 54% of the time compared with 85% with Moderna’s.

Dr. Scobie noted that Pfizer’s waning efficacy may have something to do with the fact that it uses a lower dosage than Moderna’s. Pfizer’s recommended dosing interval is also shorter – 3 weeks compared with 4 weeks for Moderna’s. Stretching the time between shots has been shown to boost vaccine effectiveness, she said.

New data from the Mayo clinic, published ahead of peer review, also suggest that Pfizer’s protection may be fading more quickly than Moderna’s. 

In February, both shots were nearly 100% effective at preventing the SARS-CoV-2 infection, but by July, against Delta, Pfizer’s efficacy had dropped to somewhere between 13% and 62%, while Moderna’s was still effective at preventing infection between 58% and 87% of the time.

In July, Pfizer’s was between 24% and 94% effective at preventing hospitalization with a COVID-19 infection and Moderna’s was between 33% and 96% effective at preventing hospitalization.

While that may sound like cause for concern, Dr. Scobie noted that, as of August 2, severe COVD-19 outcomes after vaccination are still very rare. Among 164 million fully vaccinated people in the United States there have been about 7,000 hospitalizations and 1,500 deaths; nearly three out of four of these have been in people over the age of 65.

The ACIP will next meet on August 24 to focus solely on the COVID-19 vaccines.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

The Food and Drug Administration has approved an oral solution of calcium, magnesium, potassium, and sodium oxybates (Xywav) for the treatment of idiopathic hypersomnia in adults, the company announced in a news release.

It marks the second approval for Xywav. The FDA approved it last year for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy as young as 7 years of age.

This recent approval is the first for a treatment for idiopathic hypersomnia.

“Idiopathic hypersomnia can have a significant impact on the social, educational, and occupational functioning of people living with the condition,” Diane Powell, board chair and CEO of the Hypersomnia Foundation, noted in the release.

This FDA approval “is a major milestone for the entire idiopathic hypersomnia community as Xywav becomes the first medicine approved to manage this chronic sleep disorder,” said Ms. Powell.

Low sodium oxybate product

Xywav is a novel oxybate product with a unique composition of cations. It contains 92% less sodium than sodium oxybate (Xyrem) at the recommended adult dosage range of 6 to 9 g, the company noted in a news release.

An estimated 37,000 people in the United States have been diagnosed with idiopathic hypersomnia, a neurologic sleep disorder characterized by chronic excessive daytime sleepiness.

Other symptoms of the disorder may include severe sleep inertia or sleep drunkenness (prolonged difficulty waking with frequent re-entries into sleep, confusion, and irritability), as well as prolonged, nonrestorative night-time sleep, cognitive impairment, and long and unrefreshing naps.

The approval was based on findings from a phase 3, double-blind, multicenter, placebo-controlled, randomized withdrawal study.

Results showed “statistically significant and clinically meaningful” differences compared with placebo in change in the primary endpoint of Epworth Sleepiness Scale score (P < .0001) and the secondary endpoints of Patient Global Impression of Change (P < .0001) and the Idiopathic Hypersomnia Severity Scale (P < .0001), the company reported.

The most common adverse reactions were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor.

The novel agent can be administered once or twice nightly for the treatment of idiopathic hypersomnia in adults.

“To optimize response, a patient’s health care provider may consider prescribing a twice-nightly regimen in equally or unequally divided doses at bedtime and 2.5 to 4 hours later and gradually titrate Xywav so that a patient may receive an individualized dose and regimen based on efficacy and tolerability,” the company said.

Xywav carries a boxed warning because it is a central nervous system depressant and because there is potential for abuse and misuse. The drug is only available through a risk evaluation and mitigation strategy (REMS) program.

The company plans to make Xywav available to patients with idiopathic hypersomnia later this year following implementation of the REMS program.

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

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

Therapeutic levels of heparin can have widely varying effects on COVID-19 patients depending on the severity of their disease, according to a multiplatform clinical trial that analyzed patient data from three international trials.

NYU Langone Health

COVID-19 patients in the ICU, or at least receiving ICU-level care, derived no benefit from anticoagulation with heparin, while non–critically ill COVID-19 patients – those who were hospitalized but not receiving ICU-level care – on the same anticoagulation were less likely to progress to need respiratory or cardiovascular organ support despite a slightly heightened risk of bleeding events.

Reporting in two articles published online in the New England Journal of Medicine, authors of three international trials combined their data into one multiplatform trial that makes a strong case for prescribing therapeutic levels of heparin in hospitalized patients not receiving ICU-level care were non–critically ill and critically ill.

“I think this is going to be a game changer,” said Jeffrey S. Berger, MD, ACTIV-4a co–principal investigator and co–first author of the study of non–critically ill patients. “I think that using therapeutic-dose anticoagulation should improve outcomes in the tens of thousands of patients worldwide. I hope our data can have a global impact.”
 

Outcomes based on disease severity

The multiplatform trial analyzed data from the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC); A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19 (ACTIV-4a); and Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

The trial evaluated 2,219 non–critically ill hospitalized patients, 1,181 of whom were randomized to therapeutic-dose anticoagulation; and 1,098 critically ill patients, 534 of whom were prescribed therapeutic levels of heparin.

In the critically ill patients, those on heparin were no more likely to get discharged or spend fewer days on respiratory or CV organ support – oxygen, mechanical ventilation, life support, vasopressors or inotropes – than were those on usual-care thromboprophylaxis. The investigators stopped the trial in both patient populations: in critically ill patients when it became obvious therapeutic-dose anticoagulation was having no impact; and in moderately ill patients when the trial met the prespecified criteria for the superiority of therapeutic-dose anticoagulation.

ICU patients on therapeutic-level heparin spent an average of 1 day free of organ support vs. 4 for patients on usual-care prophylactic antithrombotic drugs. The percentage of patients who survived to hospital discharge was similar in the therapeutic-level and usual-care critically ill patients: 62.7% and 64.5%, respectively. Major bleeding occurred in 3.8% and 2.8%, respectively. Demographic and clinical characteristics were similar between both patient groups.

However, in non–critically ill patients, therapeutic levels of heparin resulted in a marked improvement in outcomes. The researchers estimated that, for every 1,000 hospitalized patients with what they labeled moderate disease, an initial treatment with therapeutic-dose heparin resulted in 40 additional patients surviving compared to usual-care thromboprophylaxis.

The percentages of patients not needing organ support before hospital discharge was 80.2% on therapeutic-dose heparin and 76.4% on usual-care therapy. In terms of adjusted odds ratio, the anticoagulation group had a 27% improved chance of not needing daily organ support.

Those improvements came with an additional seven major bleeding events per 1,000 patients. That broke down to a rate of 1.9% in the therapeutic-dose and 0.9% in the usual-care patients.

As the Delta variant of COVID-19 spreads, Patrick R. Lawler, MD, MPH, principal investigator of the ATTACC trial, said there’s no reason these findings shouldn’t apply for all variants of the disease.

University of Toronto

Dr. Lawler, a physician-scientist at Peter Munk Cardiac Centre at Toronto General Hospital, noted that the multiplatform study did not account for disease variant. “Ongoing clinical trials are tracking the variant patients have or the variants that are most prevalent in an area at that time,” he said. “It may be easier in future trials to look at that question.”
 

Explaining heparin’s varying effects

The study did not specifically sort out why moderately ill patients fared better on heparin than their critically ill counterparts, but Dr. Lawler speculated on possible reasons. “One might be that the extent of illness severity is too extreme in the ICU-level population for heparin to have a beneficial extent,” he said.

He acknowledged that higher rates of macrovascular thrombosis, such as venous thromboembolism, in ICU patients would suggest that heparin would have a greater beneficial effect, but, he added, “it may also suggest how advanced that process is, and perhaps heparin is not adequate to reverse the course at that point given relatively extensive thrombosis and associate organ failure.”

As clinicians have gained experience dealing with COVID-19, they’ve learned that infected patients carry a high burden of macro- and microthrombosis, Dr. Berger said, which may explain why critically ill patients didn’t respond as well to therapeutic levels of heparin. “I think the cat is out of the bag; patients who are severe are too ill to benefit,” he said. “I would think there’s too much microthrombosis that is already in their bodies.”

However, this doesn’t completely rule out therapeutic levels of heparin in critically ill COVID-19 patients. There are some scenarios where it’s needed, said Dr. Berger, associate professor of medicine and surgery and director of the Center for the Prevention of Cardiovascular Disease at New York University Langone Health. “Anyone who has a known clot already, like a known macrothrombosis in their leg or lung, needs to be on full-dose heparin,” he said.

That rationale can help reconcile the different outcomes in the critically and non–critically ill COVID-19 patients, wrote Hugo ten Cate, MD, PhD, of Maastricht University in the Netherlands, wrote in an accompanying editorial. But differences in the study populations may also explain the divergent outcomes, Dr. ten Cate noted.

The studies suggest that critically ill patients may need hon-heparin antithrombotic approaches “or even profibrinolytic strategies,” Dr. Cate wrote, and that the safety and effectiveness of thromboprophylaxis “remains an important question.” Nonetheless, he added, treating physicians must deal with the bleeding risk when using heparin or low-molecular-weight heparin in moderately ill COVID-19 patients.

Deepak L. Bhatt MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center, Boston, said in an interview that reconciling the two studies was “a bit challenging,” because effective therapies tend to have a greater impact in sicker patients.

“Of course, with antithrombotic therapies, bleeding side effects can sometimes overwhelm benefits in patients who are at high risk of both bleeding and ischemic complications, though that does not seem to be the explanation here,” Dr. Bhatt said. “I do think we need more data to clarify exactly which COVID patients benefit from various antithrombotic regimens, and fortunately, there are other ongoing studies, some of which will report relatively soon.”

He concurred with Dr. Berger that patients who need anticoagulation should receive it “apart from their COVID status,” Dr. Bhatt said. “Sick, hospitalized patients with or without COVID should receive appropriate prophylactic doses of anticoagulation.” However, he added, “Whether we should routinely go beyond that in COVID-positive inpatients, I think we need more data.”

The ATTACC platform received grants from the Canadian Institutes of Health Research and several other research foundations. The ACTIV-4a platform received funding from the National Heart, Lung, and Blood Institute. REMAP-CAP received funding from the European Union and several international research foundations, as well as Amgen and Eisai.

Dr. Lawler had no relationships to disclose. Dr. Berger disclosed receiving grants from the NHLBI, and financial relationships with AstraZeneca, Janssen, and Amgen outside the submitted work. Dr. ten Cate reported relationships with Alveron, Coagulation Profile, Portola/Alexion, Bayer, Pfizer, Stago, Leo Pharma, Daiichi, and Gilead/Galapagos. Dr. Bhatt is chair of the data safety and monitoring board of the FREEDOM COVID anticoagulation clinical trial.

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The FDA has authorized a third dose of either the Pfizer or Moderna COVID-19 vaccines for people with compromised immune systems.

The decision, which came late on Aug. 12, was not unexpected and a Centers for Disease Control and Prevention (CDC) panel meeting Aug. 13 is expected to approve directions to doctors and health care providers on who should receive the booster shot.

“The country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease. After a thorough review of the available data, the FDA determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines,” acting FDA Commissioner Janet Woodcock, MD, said in a statement.

Those eligible for a third dose include solid organ transplant recipients, those undergoing cancer treatments, and people with autoimmune diseases that suppress their immune systems.

Meanwhile, White House officials said Aug. 12 they “have supply and are prepared” to give all U.S. residents COVID-19 boosters -- which, as of now, are likely to be authorized first only for immunocompromised people.

“We believe sooner or later you will need a booster,” Anthony Fauci, MD, said at a news briefing Aug. 12. “Right now, we are evaluating this on a day-by-day, week-by-week, month-by-month basis.”

He added: “Right at this moment, apart from the immunocompromised -- elderly or not elderly -- people do not need a booster.” But, he said, “We’re preparing for the eventuality of doing that.”

White House COVID-19 Response Coordinator Jeff Zients said officials “have supply and are prepared” to at some point provide widespread access to boosters.

The immunocompromised population is very small -- less than 3% of adults, said CDC Director Rochelle Walensky, MD.

Meanwhile, COVID-19 rates continue to rise. Dr. Walensky reported that the 7-day average of daily cases is 132,384 -- an increase of 24% from the previous week. Average daily hospitalizations are up 31%, at 9,700, and deaths are up to 452 -- an increase of 22%.

In the past week, Florida has had more COVID-19 cases than the 30 states with the lowest case rates combined, Mr. Zients said. Florida and Texas alone have accounted for nearly 40% of new hospitalizations across the country.


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

The U.S. Food and Drug Administration (FDA) could green-light a booster dose of the COVID-19 mRNA vaccines for people with weakened immune systems within the next two days, according to multiple media reports.

The agency, along with the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health, is working through the details of how booster doses for this population would work, and could authorize a third dose of both the Pfizer and Moderna vaccines as early as Aug. 12, Politico reports.

About 2.7% of adults in the United States are immunocompromised, according to the CDC. This group includes people who have cancer, have received solid organ or stem cell transplants, have genetic conditions that weaken the immune function, have HIV, or are people with health conditions that require treatment with medications that turn down immune function, such as rheumatoid arthritis. 

Immune function also wanes with age, so the FDA could consider boosters for the elderly.

New research shows that between one-third and one-half of immunocompromised patients who didn’t develop detectable levels of virus-fighting antibodies after two doses of a COVID vaccine will respond to a third dose. 

A committee of independent experts that advises the CDC on the use of vaccines in the United States had previously signaled its support for giving boosters to those who are immunocompromised, but noted that it couldn’t officially recommend the strategy until the FDA had updated its emergency-use authorization for the shots or granted them a full biologics license, or “full approval.”

It’s unclear which mechanism the FDA might use, or exactly who will be eligible for the shots.

The United States would follow other nations such as Israel, France, the United Kingdom, and Germany in planning for or authorizing boosters for some vulnerable individuals.

The World Health Organization (WHO) has voiced strong opposition to the use of boosters in wealthy countries while much of the world still doesn’t have access to these lifesaving therapies. The WHO has asked wealthy nations to hold off on giving boosters until at least the end of September to give more people the opportunity to get a first dose.

The CDC’s Advisory Committee on Immunization Practices (ACIP) meets again on Aug. 13 and is expected to discuss booster doses for this population of patients. The ACIP officially makes recommendations on the use of vaccines to the nation’s doctors.

The committee’s recommendation ensures that a vaccine will be covered by public and private insurers. Statutory vaccination requirements are also made based on the ACIP’s recommendations.

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

The U.S. Food and Drug Administration (FDA) could green-light a booster dose of the COVID-19 mRNA vaccines for people with weakened immune systems within the next two days, according to multiple media reports.

The agency, along with the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health, is working through the details of how booster doses for this population would work, and could authorize a third dose of both the Pfizer and Moderna vaccines as early as Aug. 12, Politico reports.

About 2.7% of adults in the United States are immunocompromised, according to the CDC. This group includes people who have cancer, have received solid organ or stem cell transplants, have genetic conditions that weaken the immune function, have HIV, or are people with health conditions that require treatment with medications that turn down immune function, such as rheumatoid arthritis. 

Immune function also wanes with age, so the FDA could consider boosters for the elderly.

New research shows that between one-third and one-half of immunocompromised patients who didn’t develop detectable levels of virus-fighting antibodies after two doses of a COVID vaccine will respond to a third dose. 

A committee of independent experts that advises the CDC on the use of vaccines in the United States had previously signaled its support for giving boosters to those who are immunocompromised, but noted that it couldn’t officially recommend the strategy until the FDA had updated its emergency-use authorization for the shots or granted them a full biologics license, or “full approval.”

It’s unclear which mechanism the FDA might use, or exactly who will be eligible for the shots.

The United States would follow other nations such as Israel, France, the United Kingdom, and Germany in planning for or authorizing boosters for some vulnerable individuals.

The World Health Organization (WHO) has voiced strong opposition to the use of boosters in wealthy countries while much of the world still doesn’t have access to these lifesaving therapies. The WHO has asked wealthy nations to hold off on giving boosters until at least the end of September to give more people the opportunity to get a first dose.

The CDC’s Advisory Committee on Immunization Practices (ACIP) meets again on Aug. 13 and is expected to discuss booster doses for this population of patients. The ACIP officially makes recommendations on the use of vaccines to the nation’s doctors.

The committee’s recommendation ensures that a vaccine will be covered by public and private insurers. Statutory vaccination requirements are also made based on the ACIP’s recommendations.

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

The U.S. Food and Drug Administration (FDA) could green-light a booster dose of the COVID-19 mRNA vaccines for people with weakened immune systems within the next two days, according to multiple media reports.

The agency, along with the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health, is working through the details of how booster doses for this population would work, and could authorize a third dose of both the Pfizer and Moderna vaccines as early as Aug. 12, Politico reports.

About 2.7% of adults in the United States are immunocompromised, according to the CDC. This group includes people who have cancer, have received solid organ or stem cell transplants, have genetic conditions that weaken the immune function, have HIV, or are people with health conditions that require treatment with medications that turn down immune function, such as rheumatoid arthritis. 

Immune function also wanes with age, so the FDA could consider boosters for the elderly.

New research shows that between one-third and one-half of immunocompromised patients who didn’t develop detectable levels of virus-fighting antibodies after two doses of a COVID vaccine will respond to a third dose. 

A committee of independent experts that advises the CDC on the use of vaccines in the United States had previously signaled its support for giving boosters to those who are immunocompromised, but noted that it couldn’t officially recommend the strategy until the FDA had updated its emergency-use authorization for the shots or granted them a full biologics license, or “full approval.”

It’s unclear which mechanism the FDA might use, or exactly who will be eligible for the shots.

The United States would follow other nations such as Israel, France, the United Kingdom, and Germany in planning for or authorizing boosters for some vulnerable individuals.

The World Health Organization (WHO) has voiced strong opposition to the use of boosters in wealthy countries while much of the world still doesn’t have access to these lifesaving therapies. The WHO has asked wealthy nations to hold off on giving boosters until at least the end of September to give more people the opportunity to get a first dose.

The CDC’s Advisory Committee on Immunization Practices (ACIP) meets again on Aug. 13 and is expected to discuss booster doses for this population of patients. The ACIP officially makes recommendations on the use of vaccines to the nation’s doctors.

The committee’s recommendation ensures that a vaccine will be covered by public and private insurers. Statutory vaccination requirements are also made based on the ACIP’s recommendations.

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

The U.S. Food and Drug Administration has approved a new enzyme replacement therapy, avalglucosidase alfa (Nexviazyme, Genzyme), for patients aged 1 year and older with late-onset Pompe disease.

Pompe disease is a rare genetic disease that occurs in an estimated 1 in 40,000 births. It is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which leads to a buildup of glycogen in skeletal and cardiac muscle cells, causing muscle weakness and premature death from respiratory failure or heart failure.

Nexviazyme, administered by intravenous infusion every 2 weeks, supplements GAA and helps reduce glycogen accumulation.

The approval of this product “brings patients with Pompe disease another enzyme replacement therapy option for this rare disease,” said Janet Maynard, MD, deputy director, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research, in a news release.

In 2010, the FDA approved alglucosidase alfa (Lumizyme) for the treatment of late-onset Pompe disease.

“The FDA will continue to work with stakeholders to advance the development of additional new, effective, and safe therapies for rare diseases, including Pompe disease,” said Dr. Maynard.

The approval is based on positive phase 3 data that demonstrated improvements in key disease burden measures, including respiratory function and walking disease, and that established the drug’s safety profile, Genzyme said in a news release.

The most common side effects were headache, fatigue, diarrhea, nausea, joint pain, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.

Serious reactions included hypersensitivity reactions, such as anaphylaxis, and infusion-associated reactions, including respiratory distress, chills, and pyrexia.

Patients susceptible to fluid volume overload or those with compromised cardiac or respiratory function may be at risk for serious acute cardiorespiratory failure.

The FDA granted Nexviazyme orphan drug designation, priority review, and breakthrough status.

Genzyme expects the new therapy to be available in the United States in the coming weeks and said it will be priced on par with Lumizyme.

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

The U.S. Food and Drug Administration has approved a new enzyme replacement therapy, avalglucosidase alfa (Nexviazyme, Genzyme), for patients aged 1 year and older with late-onset Pompe disease.

Pompe disease is a rare genetic disease that occurs in an estimated 1 in 40,000 births. It is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which leads to a buildup of glycogen in skeletal and cardiac muscle cells, causing muscle weakness and premature death from respiratory failure or heart failure.

Nexviazyme, administered by intravenous infusion every 2 weeks, supplements GAA and helps reduce glycogen accumulation.

The approval of this product “brings patients with Pompe disease another enzyme replacement therapy option for this rare disease,” said Janet Maynard, MD, deputy director, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research, in a news release.

In 2010, the FDA approved alglucosidase alfa (Lumizyme) for the treatment of late-onset Pompe disease.

“The FDA will continue to work with stakeholders to advance the development of additional new, effective, and safe therapies for rare diseases, including Pompe disease,” said Dr. Maynard.

The approval is based on positive phase 3 data that demonstrated improvements in key disease burden measures, including respiratory function and walking disease, and that established the drug’s safety profile, Genzyme said in a news release.

The most common side effects were headache, fatigue, diarrhea, nausea, joint pain, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.

Serious reactions included hypersensitivity reactions, such as anaphylaxis, and infusion-associated reactions, including respiratory distress, chills, and pyrexia.

Patients susceptible to fluid volume overload or those with compromised cardiac or respiratory function may be at risk for serious acute cardiorespiratory failure.

The FDA granted Nexviazyme orphan drug designation, priority review, and breakthrough status.

Genzyme expects the new therapy to be available in the United States in the coming weeks and said it will be priced on par with Lumizyme.

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

The U.S. Food and Drug Administration has approved a new enzyme replacement therapy, avalglucosidase alfa (Nexviazyme, Genzyme), for patients aged 1 year and older with late-onset Pompe disease.

Pompe disease is a rare genetic disease that occurs in an estimated 1 in 40,000 births. It is caused by a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which leads to a buildup of glycogen in skeletal and cardiac muscle cells, causing muscle weakness and premature death from respiratory failure or heart failure.

Nexviazyme, administered by intravenous infusion every 2 weeks, supplements GAA and helps reduce glycogen accumulation.

The approval of this product “brings patients with Pompe disease another enzyme replacement therapy option for this rare disease,” said Janet Maynard, MD, deputy director, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine, in the FDA’s Center for Drug Evaluation and Research, in a news release.

In 2010, the FDA approved alglucosidase alfa (Lumizyme) for the treatment of late-onset Pompe disease.

“The FDA will continue to work with stakeholders to advance the development of additional new, effective, and safe therapies for rare diseases, including Pompe disease,” said Dr. Maynard.

The approval is based on positive phase 3 data that demonstrated improvements in key disease burden measures, including respiratory function and walking disease, and that established the drug’s safety profile, Genzyme said in a news release.

The most common side effects were headache, fatigue, diarrhea, nausea, joint pain, dizziness, myalgia, pruritus, vomiting, dyspnea, erythema, paresthesia, and urticaria.

Serious reactions included hypersensitivity reactions, such as anaphylaxis, and infusion-associated reactions, including respiratory distress, chills, and pyrexia.

Patients susceptible to fluid volume overload or those with compromised cardiac or respiratory function may be at risk for serious acute cardiorespiratory failure.

The FDA granted Nexviazyme orphan drug designation, priority review, and breakthrough status.

Genzyme expects the new therapy to be available in the United States in the coming weeks and said it will be priced on par with Lumizyme.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

The Food and Drug Administration has cleared the FreeStyle Libre 2 iOS application for use with compatible iPhones.

The new app works with the FreeStyle Libre 2 with optional glucose alarms, which was approved in the United States in June 2020 for people with diabetes aged 4 years and older.

Until now, it was only a reader device with no app compatibility. The older FreeStyle Libre 14-day, available in the United States since July 2018, has both a reader and an app, but not optional alarms.

The new app, which will soon be available for download from the App Store, enables users to view glucose readings on their iPhones and allows for caregivers or other individuals to remotely monitor the patient’s glucose levels and receive real-time alarms via the LibreLinkUp app.

Worn for 14 days before replacement is needed, the FreeStyle Libre 2 is the longest-lasting integrated continuous glucose monitoring (iCGM) sensor currently on the market. The first iCGM, the Dexcom G6, is worn for 10 days.

The Libre 2 is available at pharmacies, typically at a lower cost than other CGM systems based on a list price comparison. The actual cost for patients varies depending on insurance coverage.

Abbott has secured partial or full reimbursement for the FreeStyle Libre system in 38 countries, including Canada, France, Germany, Japan, the United Kingdom, and the United States.

The FreeStyle Libre 3 is approved for use in the European Union.

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

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

A Food and Drug Administration advisory panel struggled to muster support for marketing clearance of the TriGuard 3 (Keystone Heart) device for use during transcatheter aortic valve replacement (TAVR).

The Circulatory Systems Devices Panel of the Medical Devices Advisory Committee took no vote when it met Aug. 3, but weighed evidence for a proposed indication for the device “to minimize the risk of cerebral damage by deflecting embolic debris away from the cerebral circulation” during TAVR.

“While this device may deflect some debris, the data would suggest it may also create issues,” said Keith B. Allen, MD, director of surgical research at the Mid America Heart & Lung Surgeons, Kansas City, Mo. “I am really concerned that our desire and the emotion that surrounds preventing stroke are not being supported by the data.”

TriGuard 3 received CE Mark in Europe in March 2020. It was submitted for 510(k) clearance and seeks to prove substantial equivalence to the predicate Sentinel device (Claret Medical), currently the only approved embolic protection device in the United States.

The device is designed to cover all three major aortic vessels (innominate, left carotid, and left subclavian arteries) and is delivered transfemorally through an 8F sheath, whereas the Sentinel is positioned within the branch vessels, doesn’t cover the left subclavian artery, and is introduced through the radial or brachial artery via a 6F sheath.

TriGuard 3 faced an uphill battle, however, after failing to meet the primary composite efficacy endpoint in the REFLECT phase 2 trial (P = .857), with numeric trends showing higher all-cause mortality or any stroke at 30 days (9.8% vs. 6.7%) than pooled control subjects without embolic protection.

Rates for other components of the endpoint also trended higher with the device: National Institutes of Stroke Stroke Scale score worsening 2-5 days after the procedure, cerebral ischemic lesions on MRI 2-5 days after the procedure, and total cerebral ischemic lesion volume.

The Sentinel device was approved in 2017 after it failed to meet its primary efficacy endpoint of new brain lesion volume on MRI, but death and stroke rates favored the device over control, the panel pointed out.

The sponsor provided additional analyses in the per treatment (PT) population, defined as those with complete three-vessel coverage in at least two of three procedural time points. Compared with pooled control subjects, most of the imaging endpoints favored the TriGuard 3 device, but clinical neurologic event rates continued to favor the control group.

“The data used to demonstrate efficacy are all based on the PT subpopulation of the whole population, and those have to be considered promissory data,” said John Hirshfeld, MD, emeritus professor, University of Pennsylvania, Philadelphia. “This is the group where everything went well and for us to decide that’s achievable in the general population is speculative.”
 

Safety data

The REFLECT trial did meet its primary safety endpoint, with a 30-day major adverse cardiovascular event rate of 15.9%, compared with a performance goal of 34.4% (P < .0001).

Although prespecified, panel members pushed back, saying that the performance goal was unacceptably high, with several members remarking they’d never heard of a trial adding 9% as a “fudge factor” to a 25% historic control rate to get to the 34% performance target.

Keystone health officials noted that REFLECT was not designed to demonstrate a significant difference in the rate of primary safety events, compared with control. Instead, its purpose was to demonstrate that TriGuard 3 did not increase the risk associated with a TAVR procedure.

The TriGuard 3 device was successfully placed and retrieved in 100% of patients, but complete coverage was not uniform, with 72% of 157 as-treated patients having complete three-vessel coverage post TAVR but 15% having no coverage.

Panel members also expressed concern over device interference during TAVR, which was reported in nearly 10% of all TriGuard patients.

The TriGuard 3 group had 11 major vascular complications, 2 directly related to the device, and 3 stage 3 acute kidney injuries, whereas neither complication occurred in the control group.

Throughout the 9-hour hearing, the panel wrestled with what was described as a highly select patient group and small patient numbers that made it difficult to interpret observed differences. The trial involved 157 TriGuard 3 patients (including 41 from the roll-in phase) and 119 control subjects pooled from phase 2 of the trial (n = 57) and from phase 1 using the early-stage TriGuard HDH device (n = 57).

Pieter Stella, MD, PhD, Utrecht (the Netherlands) Medical Center, also presented “real-world” evidence from 75 patients in the Netherlands using the latest iteration of the device available in Europe with updates to the crimper and additional training materials to prevent the device from torquing during delivery. No strokes were reported, one patient had a transient ischemic attack (TIA), and two patients had a dissection, which resolved without sequelae.

Ralph Brindis, MD, MPH, professor of medicine, University of California, San Francisco, countered that there were only three experienced operators from a single center and that the stroke incidence was physician reported, “not data we can really embrace.”

There was much debate over why enrollment in phase 2 of the RHYTHM trial was temporarily paused in February 2019, briefly restarted, and then prematurely stopped in April 2019.

FDA officials said the study was paused at the recommendation of the data monitoring committee (DMC) because rates of safety events were different between patients and control subjects and operational errors called into question the accuracy of the data being reviewed. Ultimately, both the DMC and FDA recommended study suspension.

During the public hearing, TAVR pioneer Alain Cribier, MD, University of Rouen’s Charles Nicolle Hospital, Mont-Saint-Aignan, France, said the TriGuard 3 is of interest because it can be used with minimal need for manipulation and complete coverage of the cerebral vessels that is achieved by diverting rather than capturing debris. “The rapid and exponential growth of TAVR procedures demands safe TAVR interventions and the use of cerebral protection devices is a step in this direction.”

Others took a dim view. “Given that the Sentinel device has not demonstrated benefit on clinical outcomes, there is significant concern about similar devices, such as the TriGuard 3, providing clinical benefit,” Rita Redberg, MD, Sanket Dhruva, MD, and Robin Ji, University of California, San Francisco, wrote in a letter submitted to the panel.

Commenting further, they added: “With the results from the REFLECT II trial demonstrating no evidence for clinical outcome benefit in TAVR patients, and numerically higher rates for stroke risk, mortality, bleeding risk, and other dangerous adverse complications among those treated, it is concerning and dangerous for patient safety that the TriGUARD 3 cerebral embolic protection device is being considered for FDA 510(k) clearance.”

The FDA panel members reported no financial relationships.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”