News from the FDA/CDC

More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

[email protected]

More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

[email protected]

More children aged 12-15 years already have received at least one dose of a COVID-19 vaccine than have 16- and 17-year-olds, based on data from the Centers for Disease Control and Prevention.

As of May 30, almost 2.89 million children aged 12-15 years had received at least one dose, compared with nearly 2.73 million children aged 16-17, with those figures representing increases of 31.6% and 6.6% in the past week, respectively. Since the overall size of the 12-15 population is much larger, however, the proportion vaccinated is still smaller: 19.5% to 36.4%, according to the CDC’s COVID Data Tracker.

A look at full vaccination status shows that only 0.7% of those aged 12-15 years have received both doses of a two-dose vaccine or one dose of the single-shot variety, compared with 24% of those aged 16-17. For the country as a whole, 50.5% of all ages have received at least one dose and 40.7% are fully vaccinated, the CDC said.

Children aged 12-15 represent the largest share of the U.S. population (23.4%) initiating vaccination in the 14 days ending May 30, while children aged 16-17 made up just 4.5% of those getting their first dose. The younger group’s later entry into the vaccination pool shows up again when looking at completion rates, though, representing just 0.4% of all Americans who reached full vaccination during that same 14-day period, compared with 4.6% of the older children, the CDC data show.

Not all states are reporting data such as age for vaccine recipients, the CDC noted, and there are other variables that affect data collection. “Demographic data ... might differ by populations prioritized within each state or jurisdiction’s vaccination phase. Every geographic area has a different racial and ethnic composition, and not all are in the same vaccination phase,” the CDC said.

[email protected]

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The benefits of COVID-19 vaccination “enormously outweigh” the rare possible risk for heart-related complications, including myocarditis, the American Heart Association/American Stroke Association (ASA) says in new statement.

The message follows a Centers for Disease Control and Prevention report that the agency is monitoring the Vaccine Adverse Events Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for cases of myocarditis that have been associated with the mRNA vaccines against SARS-CoV-2 from Pfizer and Moderna.

The “relatively few” reported cases myocarditis in adolescents or young adults have involved males more often than females, more often followed the second dose rather than the first, and were usually seen in the 4 days after vaccination, the CDC’s COVID-19 Vaccine Safety Technical Work Group (VaST) found.

“Most cases appear to be mild, and follow-up of cases is ongoing,” the CDC says. “Within CDC safety monitoring systems, rates of myocarditis reports in the window following COVID-19 vaccination have not differed from expected baseline rates.”

In their statement, the AHA/ASA “strongly urge” all adults and children 12 years and older to receive a COVID-19 vaccine as soon as possible.

“The evidence continues to indicate that the COVID-19 vaccines are nearly 100% effective at preventing death and hospitalization due to COVID-19 infection,” the groups say.

Although the investigation of cases of myocarditis related to COVID-19 vaccination is ongoing, the AHA/ASA notes that myocarditis is typically the result of an actual viral infection, “and it is yet to be determined if these cases have any correlation to receiving a COVID-19 vaccine.”

“We’ve lost hundreds of children, and there have been thousands who have been hospitalized, thousands who developed an inflammatory syndrome, and one of the pieces of that can be myocarditis,” Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation (RWJF), said today on ABC’s Good Morning America.

Still, “from my perspective, the risk of COVID is so much greater than any theoretical risk from the vaccine,” said Dr. Besser, former acting director of the CDC.

The symptoms that can occur after COVID-19 vaccination include tiredness, headache, muscle pain, chills, fever, and nausea, reminds the AHA/ASA statement. Such symptoms would “typically appear within 24-48 hours and usually pass within 36-48 hours after receiving the vaccine.”

All health care providers should be aware of the “very rare” adverse events that could be related to a COVID-19 vaccine, including myocarditis, blood clots, low platelets, and symptoms of severe inflammation, it says.

“Health care professionals should strongly consider inquiring about the timing of any recent COVID vaccination among patients presenting with these conditions, as needed, in order to provide appropriate treatment quickly,” the statement advises.

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

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

The Food and Drug Administration is recommending patients and caregivers keep cell phones and smart watches at least 6 inches away from implanted medical devices, such as pacemakers and defibrillators.

Terry Rudd/MDedge News

The warning, published on May 13, comes on the heels of recent research reporting that high–field strength magnets in newer smartphones may cause some implanted medical devices to switch to “magnet mode” and suspend normal lifesaving operations until the magnet is moved away.

This, for example, may cause a cardiac defibrillator to be unable to detect tachycardia events, the agency noted. The magnets may also change the operational mode such as turning on asynchronous mode in a pacemaker.

“The FDA is aware of published articles which describe the effect that sufficiently strong magnetic fields can turn on the magnetic safe mode when in close contact,” it said. “The FDA also conducted its own testing on some products that use the high–field strength magnet feature and have confirmed the magnetic field is both consistent with the publications and strong enough to turn on the magnetic safety mode of the medical devices in question.”

The FDA said it believes the risk to patients is low and is not aware of any adverse events associated with this issue at this time.

The American Heart Association has also cautioned that magnetic fields can inhibit the pulse generators for implantable cardioverter defibrillators and pacemakers.

The FDA offered the following simple precautions for individuals with implanted medical devices:

• Keep the consumer electronics, such as certain cell phones and smart watches, 6 inches away from implanted medical devices.
• Do not carry consumer electronics in a pocket over the medical device.
• Check your device using your home monitoring system, if you have one.
• Talk to your health care provider if you are experiencing any symptoms or have questions regarding magnets in consumer electronics and implanted medical devices.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

The Food and Drug Administration on May 10 granted emergency use authorization (EUA) for the Pfizer coronavirus vaccine to be given to children 12-15 years old.  

The much-expected decision increases the likelihood that schools in the United States will fully reopen in the fall – a goal of both the Biden and Trump administrations.

Acting FDA Commissioner Janet Woodcock, MD, called the decision “a significant step” in “returning to a sense of normalcy.”

“Today’s action allows for a younger population to be protected from COVID-19, bringing us closer to returning to a sense of normalcy and to ending the pandemic,” she said in a statement. “Parents and guardians can rest assured that the agency undertook a rigorous and thorough review of all available data, as we have with all of our COVID-19 vaccine emergency use authorizations.”

The Pfizer adolescent vaccine is not yet a done deal, though.

Next, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will decide on May 12 whether to recommend use of the vaccine in this age group. After that, CDC Director Rochelle Walensky, MD, will decide whether to give the green light for the vaccine to be administered to that age group.

The FDA action on May 10 amends the Dec. 11, 2020, emergency use authorization that allowed the Pfizer vaccine to be given to people 16 and older. Pfizer was the first company to receive an EUA for its adult vaccine and is the first to receive authorization for its adolescent vaccine. Pfizer is conducting clinical trials on much younger children, too.

The Moderna and Johnson & Johnson vaccines are authorized for people 18 and up. Moderna also has launched clinical trials in children.

Most health experts have said the United States needs to vaccinate children before the COVID-19 pandemic can truly be brought under control. The 12- to 15-year-old group represents 17 million people, about 5% of the population. Thus far, 58% of U.S. adults have had at least one dose of a vaccine and 34.8% of all Americans are fully vaccinated.

American Academy of Pediatrics President Lee Savio Beers, MD, praised the agency’s decision, calling it a “critically important step in bringing life-saving vaccines to children and adolescents. Our youngest generations have shouldered heavy burdens over the past year, and the vaccine is a hopeful sign that they will be able to begin to experience all the activities that are so important for their health and development.”

President Joe Biden recently announced a new strategy for expanding vaccinations in which vaccinating 12- to 15-year-olds was a key component. He said the administration was ready to ship the adolescent vaccine directly to pharmacies and pediatricians to speed up the vaccination rate.

In March, Anthony S. Fauci, MD, told a Senate committee, “We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape. … We ultimately would like to get and have to get children into that mix.” 

Pfizer submitted data to the FDA in late March showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12-15 in clinical trials.

Though most children have milder symptoms when infected with the coronavirus, about 1.5 million cases in children aged 11-17 were reported to the CDC between March 1, 2020, and April 30 of this year, the FDA news release said.

Albert Bourla, CEO of Pfizer, tweeted that “today brings very encouraging news for families and adolescents across the United States.

“While this is a meaningful step forward, we are still in a critical period of combating #COVID19 around the world. In the coming weeks, we hope to continue to receive authorizations from global regulators to support worldwide vaccination efforts,” he said. 

“It’s essential for children to be vaccinated against COVID-19. According to data compiled by the AAP and Children’s Hospital Association, more than 3.8 million children have tested positive for COVID-19 in the United States since the start of the pandemic,” said Dr. Savio Beers. “While fewer children than adults have suffered the most severe disease, this is not a benign disease in children. Thousands of children have been hospitalized, and hundreds have died. We will soon have a very safe, highly effective vaccine that can prevent so much suffering. I encourage parents to talk with their pediatricians about how to get the vaccine for their adolescents as soon as they are eligible.”

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

The Food and Drug Administration on May 10 granted emergency use authorization (EUA) for the Pfizer coronavirus vaccine to be given to children 12-15 years old.  

The much-expected decision increases the likelihood that schools in the United States will fully reopen in the fall – a goal of both the Biden and Trump administrations.

Acting FDA Commissioner Janet Woodcock, MD, called the decision “a significant step” in “returning to a sense of normalcy.”

“Today’s action allows for a younger population to be protected from COVID-19, bringing us closer to returning to a sense of normalcy and to ending the pandemic,” she said in a statement. “Parents and guardians can rest assured that the agency undertook a rigorous and thorough review of all available data, as we have with all of our COVID-19 vaccine emergency use authorizations.”

The Pfizer adolescent vaccine is not yet a done deal, though.

Next, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will decide on May 12 whether to recommend use of the vaccine in this age group. After that, CDC Director Rochelle Walensky, MD, will decide whether to give the green light for the vaccine to be administered to that age group.

The FDA action on May 10 amends the Dec. 11, 2020, emergency use authorization that allowed the Pfizer vaccine to be given to people 16 and older. Pfizer was the first company to receive an EUA for its adult vaccine and is the first to receive authorization for its adolescent vaccine. Pfizer is conducting clinical trials on much younger children, too.

The Moderna and Johnson & Johnson vaccines are authorized for people 18 and up. Moderna also has launched clinical trials in children.

Most health experts have said the United States needs to vaccinate children before the COVID-19 pandemic can truly be brought under control. The 12- to 15-year-old group represents 17 million people, about 5% of the population. Thus far, 58% of U.S. adults have had at least one dose of a vaccine and 34.8% of all Americans are fully vaccinated.

American Academy of Pediatrics President Lee Savio Beers, MD, praised the agency’s decision, calling it a “critically important step in bringing life-saving vaccines to children and adolescents. Our youngest generations have shouldered heavy burdens over the past year, and the vaccine is a hopeful sign that they will be able to begin to experience all the activities that are so important for their health and development.”

President Joe Biden recently announced a new strategy for expanding vaccinations in which vaccinating 12- to 15-year-olds was a key component. He said the administration was ready to ship the adolescent vaccine directly to pharmacies and pediatricians to speed up the vaccination rate.

In March, Anthony S. Fauci, MD, told a Senate committee, “We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape. … We ultimately would like to get and have to get children into that mix.” 

Pfizer submitted data to the FDA in late March showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12-15 in clinical trials.

Though most children have milder symptoms when infected with the coronavirus, about 1.5 million cases in children aged 11-17 were reported to the CDC between March 1, 2020, and April 30 of this year, the FDA news release said.

Albert Bourla, CEO of Pfizer, tweeted that “today brings very encouraging news for families and adolescents across the United States.

“While this is a meaningful step forward, we are still in a critical period of combating #COVID19 around the world. In the coming weeks, we hope to continue to receive authorizations from global regulators to support worldwide vaccination efforts,” he said. 

“It’s essential for children to be vaccinated against COVID-19. According to data compiled by the AAP and Children’s Hospital Association, more than 3.8 million children have tested positive for COVID-19 in the United States since the start of the pandemic,” said Dr. Savio Beers. “While fewer children than adults have suffered the most severe disease, this is not a benign disease in children. Thousands of children have been hospitalized, and hundreds have died. We will soon have a very safe, highly effective vaccine that can prevent so much suffering. I encourage parents to talk with their pediatricians about how to get the vaccine for their adolescents as soon as they are eligible.”

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

The Food and Drug Administration on May 10 granted emergency use authorization (EUA) for the Pfizer coronavirus vaccine to be given to children 12-15 years old.  

The much-expected decision increases the likelihood that schools in the United States will fully reopen in the fall – a goal of both the Biden and Trump administrations.

Acting FDA Commissioner Janet Woodcock, MD, called the decision “a significant step” in “returning to a sense of normalcy.”

“Today’s action allows for a younger population to be protected from COVID-19, bringing us closer to returning to a sense of normalcy and to ending the pandemic,” she said in a statement. “Parents and guardians can rest assured that the agency undertook a rigorous and thorough review of all available data, as we have with all of our COVID-19 vaccine emergency use authorizations.”

The Pfizer adolescent vaccine is not yet a done deal, though.

Next, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will decide on May 12 whether to recommend use of the vaccine in this age group. After that, CDC Director Rochelle Walensky, MD, will decide whether to give the green light for the vaccine to be administered to that age group.

The FDA action on May 10 amends the Dec. 11, 2020, emergency use authorization that allowed the Pfizer vaccine to be given to people 16 and older. Pfizer was the first company to receive an EUA for its adult vaccine and is the first to receive authorization for its adolescent vaccine. Pfizer is conducting clinical trials on much younger children, too.

The Moderna and Johnson & Johnson vaccines are authorized for people 18 and up. Moderna also has launched clinical trials in children.

Most health experts have said the United States needs to vaccinate children before the COVID-19 pandemic can truly be brought under control. The 12- to 15-year-old group represents 17 million people, about 5% of the population. Thus far, 58% of U.S. adults have had at least one dose of a vaccine and 34.8% of all Americans are fully vaccinated.

American Academy of Pediatrics President Lee Savio Beers, MD, praised the agency’s decision, calling it a “critically important step in bringing life-saving vaccines to children and adolescents. Our youngest generations have shouldered heavy burdens over the past year, and the vaccine is a hopeful sign that they will be able to begin to experience all the activities that are so important for their health and development.”

President Joe Biden recently announced a new strategy for expanding vaccinations in which vaccinating 12- to 15-year-olds was a key component. He said the administration was ready to ship the adolescent vaccine directly to pharmacies and pediatricians to speed up the vaccination rate.

In March, Anthony S. Fauci, MD, told a Senate committee, “We don’t really know what that magical point of herd immunity is, but we do know that if we get the overwhelming population vaccinated, we’re going to be in good shape. … We ultimately would like to get and have to get children into that mix.” 

Pfizer submitted data to the FDA in late March showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12-15 in clinical trials.

Though most children have milder symptoms when infected with the coronavirus, about 1.5 million cases in children aged 11-17 were reported to the CDC between March 1, 2020, and April 30 of this year, the FDA news release said.

Albert Bourla, CEO of Pfizer, tweeted that “today brings very encouraging news for families and adolescents across the United States.

“While this is a meaningful step forward, we are still in a critical period of combating #COVID19 around the world. In the coming weeks, we hope to continue to receive authorizations from global regulators to support worldwide vaccination efforts,” he said. 

“It’s essential for children to be vaccinated against COVID-19. According to data compiled by the AAP and Children’s Hospital Association, more than 3.8 million children have tested positive for COVID-19 in the United States since the start of the pandemic,” said Dr. Savio Beers. “While fewer children than adults have suffered the most severe disease, this is not a benign disease in children. Thousands of children have been hospitalized, and hundreds have died. We will soon have a very safe, highly effective vaccine that can prevent so much suffering. I encourage parents to talk with their pediatricians about how to get the vaccine for their adolescents as soon as they are eligible.”

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

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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

The Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda) in combination with other agents for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.

Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.

The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.

The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.

Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.

The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).

The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.

The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.

The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.

The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

The Food and Drug Administration could expand the use of the Pfizer COVID-19 vaccine to teens early next week, The New York Times and CNN reported, both citing unnamed officials familiar with the agency’s plans.

In late March, Pfizer submitted data to the FDA showing its mRNA vaccine was 100% effective at preventing COVID-19 infection in children ages 12 to 15. Their vaccine  is already authorized for use teens and adults ages 16 and older.

The move would make about 17 million more Americans eligible for vaccination and would be a major step toward getting both adolescents and teens back into classrooms full time by next fall.

“Across the globe, we are longing for a normal life. This is especially true for our children. The initial results we have seen in the adolescent studies suggest that children are particularly well protected by vaccination, which is very encouraging given the trends we have seen in recent weeks regarding the spread of the B.1.1.7 U.K. variant,” Ugur Sahin, CEO and co-founder of Pfizer partner BioNTech, said in a March 31 press release.

Getting schools fully reopened for in-person learning has been a goal of both the Trump and Biden administrations, but it has been tricky to pull off, as some parents and teachers have been reluctant to return to classrooms with so much uncertainty about the risk and the role of children in spreading the virus.

A recent study of roughly 150,000 school-aged children in Israel found that while kids under age 10 were unlikely to catch or spread the virus as they reentered classrooms. Older children, though, were a different story. The study found that children ages 10-19 had risks of catching the virus that were as high as adults ages 20-60.

The risk for severe illness and death from COVID-19 rises with age.

Children and teens are at relatively low risk from severe outcomes after a COVID-19 infection compared to adults, but they can catch it and some will get really sick with it, especially if they have an underlying health condition, like obesity or asthma that makes them more vulnerable.

Beyond the initial infection, children can get a rare late complication called MIS-C, that while treatable, can be severe and requires hospitalization. Emerging reports also suggest there are some kids that become long haulers in much the same way adults do, dealing with lingering problems for months after they first get sick.

As new variants of the coronavirus circulate in the United States, some states have seen big increases in the number of children and teens with COVID. In Michigan, for example, which recently dealt with a spring surge of cases dominated by the B.1.1.7 variant, cases in children and teens quadrupled in April compared to February.

Beyond individual protection, vaccinating children and teens has been seen as important to achieving strong community protection, or herd immunity, against the new coronavirus.

If the FDA expands the authorization for the Pfizer vaccine, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will likely meet to review data on the safety and efficacy of the vaccine. The committee may then vote on new recommendations for use of the vaccine in the United States.

Not everyone agrees with the idea that American adolescents, who are at relatively low risk of bad outcomes, could get access to COVID vaccines ahead of vulnerable essential workers and seniors in other parts of the world that are still fighting the pandemic with little access to vaccines.

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

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

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