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CDC recommends high-dose flu vaccines for seniors
In an online statement Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.
The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.
But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.
These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.
The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.
The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.
In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.
At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.
A version of this article first appeared on Medscape.com.
In an online statement Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.
The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.
But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.
These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.
The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.
The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.
In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.
At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.
A version of this article first appeared on Medscape.com.
In an online statement Fluzone High-Dose Quadrivalent, Flublok Quadrivalent, and Fluad Quadrivalent flu vaccines are among those specified in the release.
The organization says that these higher-dose vaccines may be more effective for the aging population, who often have difficulty mounting a strong enough immune response to protect themselves against the flu virus. People older than 65 years struggle the most during flu season and have the highest proportion of hospitalizations and deaths from flu, according to the release.
But the CDC believes that higher-dose vaccines have the potential to better protect against that danger. One study, from The New England Journal of Medicine, reported that high-dose/adjuvanted vaccines prevented flu in older patients 24% better than did lower-dose/nonadjuvanted vaccines.
These types of vaccines work by creating a larger immune response than a standard vaccine dose. In particular, adjuvanted vaccines contain an extra ingredient within them that helps the immune system produce a stronger reaction to the vaccine. These may be things like aluminum salts, which signal the body to respond faster. Higher-dose vaccines similarly promote a stronger immune response by having more particles of the target virus in their mixture. In theory, this means the body will create an enhanced response to the vaccine. For example, a higher-dose vaccine may quadruple the amount of antigens, compared with the standard dose.
The hope is that this recommendation may increase vaccine use across the board, says José Romero, MD, the director of the CDC’s National Center for Immunization and Respiratory Diseases. As quoted in the CDC announcement, Dr. Romero said that this may help reduce racial inequities in access to flu vaccines. A 2019 meta-analysis concluded that Black and Hispanic people are around 30%-40% less likely to get the flu vaccine. So increasing the access to this medication “could help reduce health disparities by making these vaccines more available to racial and ethnic minority groups,” said Dr. Romero.
The decision, spearheaded by CDC Director Rochelle Walensky, MD, follows recommendations from the Advisory Committee on Immunization Practices, which presented on this topic during a June 22 meeting. It is now part of official CDC policy and will continue to be developed as the 2022-2023 flu season approaches.
In addition, the organization says they’ll reveal more details for their plan later this summer, in their Morbidity and Mortality Weekly Report (MMWR). For now, seniors should know that they should try to get the recommended high-dose vaccines, but if they can’t, then a standard dose of whatever their provider has on hand will do.
At this point, there is still no specific vaccine recommendation for people aged under 65 years. The CDC historically avoids specifying one type of vaccine over another and says each should still be effective in younger patients.
A version of this article first appeared on Medscape.com.
FDA warns of increased risk of death with CLL, lymphoma drug
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
FDA Class I recall: Batteries for CARESCAPE 2860 Ventilator
A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.
Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.
This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.
However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.
To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.
When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.
There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.
A version of this article first appeared on Medscape.com.
This article was updated 7/6/22.
A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.
Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.
This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.
However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.
To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.
When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.
There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.
A version of this article first appeared on Medscape.com.
This article was updated 7/6/22.
A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.
Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.
This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.
However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.
To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.
When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.
There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.
A version of this article first appeared on Medscape.com.
This article was updated 7/6/22.
Children and COVID: Vaccination off to slow start for the newly eligible
New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.
In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.
The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.
That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.
The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.
The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.
New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.
In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.
The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.
That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.
The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.
The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.
New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.
In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.
The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.
That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.
The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.
The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.
FDA Volara ventilator warning upgraded to full recall
The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.
Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.
The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.
People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.
In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.
Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.
The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.
People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.
In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.
Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.
The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.
People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.
In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.
A version of this article first appeared on Medscape.com.
FDA orders Juul to stop selling E-cigarettes
The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.
“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.
“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”
The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.
The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”
Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.
“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”
Juul is expected to appeal the FDA’s decision, according to The New York Times.
In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.
Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.
In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.
The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.
Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.
Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.
Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.
In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.
A version of this article first appeared on WebMD.com .
The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.
“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.
“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”
The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.
The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”
Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.
“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”
Juul is expected to appeal the FDA’s decision, according to The New York Times.
In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.
Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.
In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.
The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.
Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.
Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.
Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.
In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.
A version of this article first appeared on WebMD.com .
The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.
“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.
“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”
The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.
The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”
Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.
“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”
Juul is expected to appeal the FDA’s decision, according to The New York Times.
In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.
Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.
In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.
The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.
Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.
Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.
Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.
In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.
A version of this article first appeared on WebMD.com .
FDA panel rejects pimavanserin for Alzheimer’s psychosis
In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.
The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).
In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.
For the current application, Acadia submitted some new analysis of those studies but limited its application to ADP, which affects up to 30% of patients with Alzheimer’s disease (AD) and currently has no approved treatment.
Committee members who opposed the application were moved by testimony from caregivers and clinicians who treat patients with ADP but ultimately decided the evidence offered by Acadia once again failed to meet the threshold needed to demonstrate efficacy for an expanded indication.
“Sometimes I struggle with a decision on an advisory committee, but not today,” Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., said of his “no” vote.
Lack of efficacy
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.
When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.
The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”
Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.
Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
Lack of diversity
The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.
In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.
When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.
“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.
Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
An unmet need
Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.
“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.
Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.
“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”
The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.
Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.
“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.
Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”
The FDA will make its final decision by August 4.
A version of this article first appeared on Medscape.com.
In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.
The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).
In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.
For the current application, Acadia submitted some new analysis of those studies but limited its application to ADP, which affects up to 30% of patients with Alzheimer’s disease (AD) and currently has no approved treatment.
Committee members who opposed the application were moved by testimony from caregivers and clinicians who treat patients with ADP but ultimately decided the evidence offered by Acadia once again failed to meet the threshold needed to demonstrate efficacy for an expanded indication.
“Sometimes I struggle with a decision on an advisory committee, but not today,” Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., said of his “no” vote.
Lack of efficacy
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.
When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.
The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”
Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.
Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
Lack of diversity
The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.
In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.
When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.
“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.
Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
An unmet need
Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.
“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.
Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.
“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”
The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.
Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.
“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.
Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”
The FDA will make its final decision by August 4.
A version of this article first appeared on Medscape.com.
In a 9-3 vote, the Psychopharmacologic Drugs Advisory Committee (PDAC) found that the drug’s manufacturer failed to offer convincing evidence of its efficacy in patients with ADP.
The June 17 rejection was the second rejection in as many years for a new indication for pimavanserin, which was approved in 2016 for Parkinson’s disease psychosis (PDP).
In April 2021, the FDA denied Acadia’s supplemental new drug application to expand the drug’s indication to include the treatment of all dementia-related psychosis, regardless of the underlying cause of dementia, citing issues with two studies the company presented as evidence of efficacy.
For the current application, Acadia submitted some new analysis of those studies but limited its application to ADP, which affects up to 30% of patients with Alzheimer’s disease (AD) and currently has no approved treatment.
Committee members who opposed the application were moved by testimony from caregivers and clinicians who treat patients with ADP but ultimately decided the evidence offered by Acadia once again failed to meet the threshold needed to demonstrate efficacy for an expanded indication.
“Sometimes I struggle with a decision on an advisory committee, but not today,” Dean Follmann, PhD, assistant director for biostatistics, National Institute of Allergy and Infectious Diseases, Bethesda, Md., said of his “no” vote.
Lack of efficacy
Pimavanserin is a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which are thought to play an important role in psychosis, schizophrenia, depression, and other neuropsychiatric disorders.
When it rejected Acadia’s original, broader application for pimavanserin for all dementia-related psychosis, the FDA found that the HARMONY phase 3 trial, previously covered by this news organization, was underpowered to assess efficacy in specific dementia patient subgroups and lacked statistical significance of efficacy in patients with AD. In addition, it noted that overall findings appeared to be driven by results in patients with Parkinson’s disease dementia, a condition already covered by the approved indication.
The FDA found that the second study, referred to in the June 17 hearing as Study 019, which was also previously reported by this news organization, was not “an adequate and well-controlled study.”
Specifically, the agency raised concerns about “protocol deviations,” such as the inclusion of patients who lacked clear documentation that psychotic symptoms developed after an AD diagnosis had been established and patients who received exclusionary medications at the time of randomization.
Discussions between Acadia and the FDA continued over the past year, with the company submitting new analyses and responses. An FDA briefing document published in advance of the committee meeting seemed to suggest the agency was satisfied with Acadia’s response.
Lack of diversity
The advisory committee disagreed, pointing to the same concerns raised last year. Members raised concerns about patient diversity in the HARMONY trial, which included an almost entirely White and mostly male study population.
In addition, although the findings at 26 weeks did demonstrate a marked improvement in psychosis symptoms overall, committee members noted that, again, those findings were largely driven by efficacy in patients with Parkinson’s disease dementia, for which the drug is already approved.
When discussing the phase 2 Study 019, the committee noted that while the study met the primary outcome of improvement in psychosis at 6 weeks, those positive responses were not found at any other timepoint in the 12-week study.
“While it might have had a positive numerical effect in the study, the evidence is really not there to support it,” Dr. Follmann said.
Dr. Follmann and other committee members called for additional trials that focus on patients with Alzheimer’s disease, have a longer follow-up, and include more gender and racial diversity in the study population. They also called for more information about any off-label use of pimavanserin for ADP since it was approved for PDP in 2016.
An unmet need
Most individuals who testified during the public comment period pleaded with the committee to vote in favor of the new indication, sharing stories of family members and patients with ADP.
“I have been caring for and studying patients with Alzheimer’s disease and other dementias for more than 30 years, and I can tell you very simply that if left untreated, psychosis has significant and sometimes devastating consequences for our patients,” said Pierre Tariot, MD, director of the Banner Alzheimer’s Institute and a research professor of psychiatry at the University of Arizona College of Medicine, Tucson, and an investigator on the HARMONY trial.
Those on the committee who voted against the application were quick to agree that lack of an approved treatment for ADP presents a hardship.
“I’m a neurologist who has cared for patients for more than 20 years,” said Madhav R. Thambisetty, MD, PhD, senior investigator for the National Institute on Aging and an adjunct professor of neurology at Johns Hopkins University School of Medicine, Baltimore. “I recognize the unmet need in the field, I just think that the unmet need should not be a justification to cut corners.”
The committee did not focus on drug safety or unmet need in its deliberations, although information on both were presented during the meeting.
Commenting on his “no” vote, PDAC member Walter S. Dunn, MD, PhD, assistant clinical professor of psychiatry at the University of California, Los Angeles, and director of Interventional Psychiatry Service at West Los Angeles Veterans Affairs Medical Center, said he hopes that the FDA will consider those issues more broadly as they complete their review.
“The questions before the committee have been narrow and precise, so I trust the agency will take a broader approach in their final decision about approval,” Dr. Dunn said.
Commenting on the decision, Howard Fillit, MD, cofounder and chief science officer, Alzheimer’s Drug Discovery Foundation, called the news disappointing, “but while the unmet need for a treatment for ADP is clear, it is vital that approved treatments meet stringent safety and efficacy criteria so we can offer patients medications with clear benefits.”
The FDA will make its final decision by August 4.
A version of this article first appeared on Medscape.com.
FDA approves risankizumab (Skyrizi) for Crohn’s disease
The U.S. Food and Drug Administration – making it the first specific anti–interleukin-23 monoclonal antibody indicated for Crohn’s disease.
The safety and efficacy of risankizumab in Crohn’s disease is supported by data from two induction clinical trials (ADVANCE and MOTIVATE) and one maintenance clinical trial (FORTIFY).
Results of the three studies were presented at the annual scientific meeting of the American College of Gastroenterology in 2021.
“In both the induction and maintenance clinical trials, a significantly greater number of adult patients saw few or no symptoms and a meaningful reduction of visible signs of intestinal inflammation, compared to placebo,” Marla Dubinsky, MD, gastroenterologist with the Mount Sinai Health System and codirector of the IBD Center at Mount Sinai, New York, said in a news release from AbbVie.
“This approval provides health care professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn’s disease,” Dr. Dubinsky said.
For the treatment of Crohn’s disease, risankizumab is dosed at 600 mg administered by intravenous infusion over at least 1 hour at week 0, 4, and 8, followed by 360 mg self-administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
Risankizumab is already approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration – making it the first specific anti–interleukin-23 monoclonal antibody indicated for Crohn’s disease.
The safety and efficacy of risankizumab in Crohn’s disease is supported by data from two induction clinical trials (ADVANCE and MOTIVATE) and one maintenance clinical trial (FORTIFY).
Results of the three studies were presented at the annual scientific meeting of the American College of Gastroenterology in 2021.
“In both the induction and maintenance clinical trials, a significantly greater number of adult patients saw few or no symptoms and a meaningful reduction of visible signs of intestinal inflammation, compared to placebo,” Marla Dubinsky, MD, gastroenterologist with the Mount Sinai Health System and codirector of the IBD Center at Mount Sinai, New York, said in a news release from AbbVie.
“This approval provides health care professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn’s disease,” Dr. Dubinsky said.
For the treatment of Crohn’s disease, risankizumab is dosed at 600 mg administered by intravenous infusion over at least 1 hour at week 0, 4, and 8, followed by 360 mg self-administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
Risankizumab is already approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration – making it the first specific anti–interleukin-23 monoclonal antibody indicated for Crohn’s disease.
The safety and efficacy of risankizumab in Crohn’s disease is supported by data from two induction clinical trials (ADVANCE and MOTIVATE) and one maintenance clinical trial (FORTIFY).
Results of the three studies were presented at the annual scientific meeting of the American College of Gastroenterology in 2021.
“In both the induction and maintenance clinical trials, a significantly greater number of adult patients saw few or no symptoms and a meaningful reduction of visible signs of intestinal inflammation, compared to placebo,” Marla Dubinsky, MD, gastroenterologist with the Mount Sinai Health System and codirector of the IBD Center at Mount Sinai, New York, said in a news release from AbbVie.
“This approval provides health care professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn’s disease,” Dr. Dubinsky said.
For the treatment of Crohn’s disease, risankizumab is dosed at 600 mg administered by intravenous infusion over at least 1 hour at week 0, 4, and 8, followed by 360 mg self-administered by subcutaneous injection at week 12, and every 8 weeks thereafter.
Risankizumab is already approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
A version of this article first appeared on Medscape.com.
FDA authorizes COVID vaccines in kids as young as 6 months
, one of the final steps in a long-awaited authorization process to extend protection to the youngest of Americans.
The agency’s move comes after a closely watched FDA advisory group vote earlier this week, which resulted in a unanimous vote in favor of the FDA authorizing both vaccines in this age group.
“The FDA’s evaluation and analysis of the safety, effectiveness, and manufacturing data of these vaccines was rigorous and comprehensive, supporting the EUAs,” the agency said in a news release.
The data show that the “known and potential benefits” of the vaccines outweigh any potential risks, the agency said.
The Moderna vaccine is authorized as a two-dose primary series in children 6 months to 17 years of age. The Pfizer vaccine is now authorized as a three-dose primary series in children 6 months up to 4 years of age. Pfizer’s vaccine was already authorized in children 5 years old and older.
Now all eyes are on the Centers for Disease Control and Prevention, which is expected to decide on the final regulatory hurdle at a meeting June 18. The CDC’s Advisory Committee on Immunization Practices has scheduled a vote on whether to give the vaccines the green light.
If ACIP gives the OK, CDC Director Rochelle Walensky, MD, MPH, is expected to issue recommendations for use shortly thereafter.
Following these final regulatory steps, parents could start bringing their children to pediatricians, family doctors, or local pharmacies for vaccination as early as June 20.
A version of this article first appeared on WebMD.com.
, one of the final steps in a long-awaited authorization process to extend protection to the youngest of Americans.
The agency’s move comes after a closely watched FDA advisory group vote earlier this week, which resulted in a unanimous vote in favor of the FDA authorizing both vaccines in this age group.
“The FDA’s evaluation and analysis of the safety, effectiveness, and manufacturing data of these vaccines was rigorous and comprehensive, supporting the EUAs,” the agency said in a news release.
The data show that the “known and potential benefits” of the vaccines outweigh any potential risks, the agency said.
The Moderna vaccine is authorized as a two-dose primary series in children 6 months to 17 years of age. The Pfizer vaccine is now authorized as a three-dose primary series in children 6 months up to 4 years of age. Pfizer’s vaccine was already authorized in children 5 years old and older.
Now all eyes are on the Centers for Disease Control and Prevention, which is expected to decide on the final regulatory hurdle at a meeting June 18. The CDC’s Advisory Committee on Immunization Practices has scheduled a vote on whether to give the vaccines the green light.
If ACIP gives the OK, CDC Director Rochelle Walensky, MD, MPH, is expected to issue recommendations for use shortly thereafter.
Following these final regulatory steps, parents could start bringing their children to pediatricians, family doctors, or local pharmacies for vaccination as early as June 20.
A version of this article first appeared on WebMD.com.
, one of the final steps in a long-awaited authorization process to extend protection to the youngest of Americans.
The agency’s move comes after a closely watched FDA advisory group vote earlier this week, which resulted in a unanimous vote in favor of the FDA authorizing both vaccines in this age group.
“The FDA’s evaluation and analysis of the safety, effectiveness, and manufacturing data of these vaccines was rigorous and comprehensive, supporting the EUAs,” the agency said in a news release.
The data show that the “known and potential benefits” of the vaccines outweigh any potential risks, the agency said.
The Moderna vaccine is authorized as a two-dose primary series in children 6 months to 17 years of age. The Pfizer vaccine is now authorized as a three-dose primary series in children 6 months up to 4 years of age. Pfizer’s vaccine was already authorized in children 5 years old and older.
Now all eyes are on the Centers for Disease Control and Prevention, which is expected to decide on the final regulatory hurdle at a meeting June 18. The CDC’s Advisory Committee on Immunization Practices has scheduled a vote on whether to give the vaccines the green light.
If ACIP gives the OK, CDC Director Rochelle Walensky, MD, MPH, is expected to issue recommendations for use shortly thereafter.
Following these final regulatory steps, parents could start bringing their children to pediatricians, family doctors, or local pharmacies for vaccination as early as June 20.
A version of this article first appeared on WebMD.com.
FDA panel votes unanimously for COVID shots for youngest kids
Federal advisers to the U.S. Food and Drug Administration voted unanimously June 15 to recommend the use of the Moderna and Pfizer-BioNTech COVID-19 vaccines in infants and young children.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA voted 21-0 to say that benefits of a two-dose series of Moderna’s mRNA vaccine outweigh risk for use in infants and children 6 months through 5 years of age.
The panel then voted 21-0 to say that benefits of a three-dose series of the Pfizer-BioNTech mRNA vaccine outweigh risk for use in infants and children 6 months through 4 years of age.
The FDA is not bound to follow the suggestions of its advisory committees, but it often does. Moderna and Pfizer are seeking to expand emergency use authorization (EUA) for their vaccines. EUAs are special clearances used to allow use of products in connection with public health crises such as the pandemic.
The Pfizer vaccine has standard, nonemergency FDA approval for use in people 16 years of age and older. The FDA also has granted EUA clearance for use of the shot in people ages 5 to 15.
The VRBPAC on June 15 recommended granting EUA clearance for Moderna’s COVID-19 vaccine for people ages 6 to 17. The Moderna vaccine already has full approval for use in people 18 years of age and older.
Many parents have been waiting for a clearance of COVID vaccines for their infants and young children, seeking protection for them at a time of continued spread of the virus.
The White House on June 9 outlined plans for making 10 million doses of COVID vaccines available for children under the age of 5 in the coming weeks.
The Centers for Disease Control and Prevention (CDC) has scheduled a June 18 meeting of its Advisory Committee on Immunization Practices, where members of that panel will vote on recommendations about use of the Moderna and Pfizer-BioNTech vaccines in infants and young children. The last step in the approval process to get shots into arms will be endorsement by the CDC director if the committee votes in favor of the vaccines.
For and against
During the public session during the June 15 FDA meeting, speakers offered varied opinions.
Some urged the panel to vote against the EUA expansion, citing concerns about risks of COVID vaccines in general.
But at the close of the meeting, top FDA vaccine official Peter Marks, MD, PhD, urged the public to be cautious about drawing conclusions from reading incident reports of side effects.
He said he has seen a “Twitter storm” during the day about claims of side effects. but stressed that the FDA has reported to the public on the rare side effects linked to the COVID vaccines, such as myocarditis, with advisories based on a review of reports of side effects. But many of these reports, gathered from the Vaccine Adverse Event Reporting System (VAERS) system, will turn out on further inspection not to be related to vaccination.
Many other speakers urged members of the panel to support expanded use of the vaccines for infants and young children. These speakers emphasized how lack of a vaccine to date has isolated young children who remain unprotected, even with about 83% of those age 5 and older in the United States having received at least one COVID shot.
Dr. Marks noted that there have been 442 deaths from COVID among children under 4 years of age during the pandemic, a number that he compared with the 78 deaths reported in the H1N1 flu. He urged the panel “to be careful that we don’t become numb to the number of pediatric deaths because of the overwhelming number of older deaths here.”
Panelist H. Cody Meissner, MD, a pediatric infectious disease specialist from Tufts University, said the vaccine should be made available -- particularly for children considered to be at high risk for complications from COVID --but health officials need to present a clear picture of the relatively low risks to children of harm from the vaccines-- and from COVID.
“That has to be communicated clearly to parents so that they can participate in the decision about vaccinating a child in this age group,” Dr. Meissner said.
The results presented June 15 from studies of the shots in younger children were less impressive than those from the initial COVID vaccine trials done in adults. This was not a surprise to panelists given the rise of the omicron variant and the evolution of the pandemic, but it still led to comments about the need for further continued study of the vaccines in young children even if they are authorized.
Consider that in 2020, Pfizer won the first EUA for a COVID vaccine of any kind with data that pegged the shot’s efficacy rate at 95%. Statisticians estimated a likely possible range, or 95% confidence interval, for the vaccine efficacy rate at 90.3% to 97.6%.
Those estimates were based on finding eight cases of COVID reported among 18,198 study participants who got the Pfizer-BioNTech shot, compared with 162 cases among the 18,325 people in the placebo group, according to the FDA review of Pifzer’s initial application.
Study data
But on June 15, FDA advisers had to consider an EUA application for which the data did not make as strong a case for the vaccine’s benefit among younger patients.
Pfizer presented what the FDA called a “preliminary descriptive analysis” of vaccine efficacy among participants in Study C4591007 who received three study vaccinations, following accrual of 10 total confirmed COVID-19 cases occurring at least 7 days after the third dose.
Looking at results for study participants ages 6 to 23 months of age, there was one case in the group that got the Pfizer-BioNTech shot and two in the placebo group, pegged as a 75.6% vaccine efficacy rate -- but one with caveats to the small numbers of cases. The 95% confidence interval for this vaccine efficacy rate was reported as-369.1% to 99.6% according to the FDA staff review.
For participants 2-4 years of age with and without evidence of prior SARS-CoV-
2 infection, there were two cases in the group that got the shot and five in the placebo group showing a vaccine efficacy rate of 82.4%, with a 95% confidence interval estimated ranging between -7.6% and 98.3%. For the combined analysis of both age groups, the efficacy rate was estimated at 80.4%, with a 95% confidence interval of 14.1% and 96.7%.
Doran Fink, MD, PhD, a top official in the FDA’s vaccines division, noted that the current EUA application for expanded pediatric use involved “some very preliminary” results that involved “a small number of cases and limited follow up time.”
But he stressed that the evidence gathered to date for the Pifzer application for use of its COVID shot in infants and young children met the threshold for conditional clearance during a crisis.
“We do feel very confident that the evidentiary standard for benefit for an EUA has been met here,” but added that more data would be needed to address questions about the efficacy of the vaccine beyond a third dose and whether an additional dose may be needed.
Pfizer also used a comparison known as “immunobridging” in support of the application. This looked at SARS- CoV-2 50% neutralizing antibody titers for the children in the age group covered by the EUA application and compared them to a randomly selected subset of 16-25-year-old participants in another study,
Key data for the pending Moderna EUA for use of its shot in infants and young children came from study P204. In it, Moderna found 51 cases of COVID among 1,511 children ages 6 months to 23 months who got the vaccines, versus 34 cases among 513 children who received a placebo, according to an FDA staff review.
That resulted in a vaccine efficacy rate pegged at 50.6%, with a 95% confidence interval of 21.4% to 68.6%.
Looking at the children ages 2 to 5 years in the P204 study, there were 119 cases out of 2,594 participants who got the shot, versus 61 cases of 858 in the placebo arm, or 7.1%. That translated to a 36.8% vaccine efficacy rate, with a confidence interval 12.5% to 54.0%.
Panelist Jay Portnoy, MD, of Children’s Mercy Hospital in Kansas City said all of the pediatricians he knows are waiting for the FDA to authorize the new uses of these vaccines in infants and young children.
“The death rate from COVID in young children may not be extremely high, but it’s absolutely terrifying to parents to have their child be sick, have to go to the hospital or even go to the emergency room or their primary care doctor because they’re sick and having trouble breathing,” said Dr. Portnoy, who served as the panel’s consumer representative.
A version of this article first appeared on WebMD.com.
This article was updated on 6/16/22.
Federal advisers to the U.S. Food and Drug Administration voted unanimously June 15 to recommend the use of the Moderna and Pfizer-BioNTech COVID-19 vaccines in infants and young children.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA voted 21-0 to say that benefits of a two-dose series of Moderna’s mRNA vaccine outweigh risk for use in infants and children 6 months through 5 years of age.
The panel then voted 21-0 to say that benefits of a three-dose series of the Pfizer-BioNTech mRNA vaccine outweigh risk for use in infants and children 6 months through 4 years of age.
The FDA is not bound to follow the suggestions of its advisory committees, but it often does. Moderna and Pfizer are seeking to expand emergency use authorization (EUA) for their vaccines. EUAs are special clearances used to allow use of products in connection with public health crises such as the pandemic.
The Pfizer vaccine has standard, nonemergency FDA approval for use in people 16 years of age and older. The FDA also has granted EUA clearance for use of the shot in people ages 5 to 15.
The VRBPAC on June 15 recommended granting EUA clearance for Moderna’s COVID-19 vaccine for people ages 6 to 17. The Moderna vaccine already has full approval for use in people 18 years of age and older.
Many parents have been waiting for a clearance of COVID vaccines for their infants and young children, seeking protection for them at a time of continued spread of the virus.
The White House on June 9 outlined plans for making 10 million doses of COVID vaccines available for children under the age of 5 in the coming weeks.
The Centers for Disease Control and Prevention (CDC) has scheduled a June 18 meeting of its Advisory Committee on Immunization Practices, where members of that panel will vote on recommendations about use of the Moderna and Pfizer-BioNTech vaccines in infants and young children. The last step in the approval process to get shots into arms will be endorsement by the CDC director if the committee votes in favor of the vaccines.
For and against
During the public session during the June 15 FDA meeting, speakers offered varied opinions.
Some urged the panel to vote against the EUA expansion, citing concerns about risks of COVID vaccines in general.
But at the close of the meeting, top FDA vaccine official Peter Marks, MD, PhD, urged the public to be cautious about drawing conclusions from reading incident reports of side effects.
He said he has seen a “Twitter storm” during the day about claims of side effects. but stressed that the FDA has reported to the public on the rare side effects linked to the COVID vaccines, such as myocarditis, with advisories based on a review of reports of side effects. But many of these reports, gathered from the Vaccine Adverse Event Reporting System (VAERS) system, will turn out on further inspection not to be related to vaccination.
Many other speakers urged members of the panel to support expanded use of the vaccines for infants and young children. These speakers emphasized how lack of a vaccine to date has isolated young children who remain unprotected, even with about 83% of those age 5 and older in the United States having received at least one COVID shot.
Dr. Marks noted that there have been 442 deaths from COVID among children under 4 years of age during the pandemic, a number that he compared with the 78 deaths reported in the H1N1 flu. He urged the panel “to be careful that we don’t become numb to the number of pediatric deaths because of the overwhelming number of older deaths here.”
Panelist H. Cody Meissner, MD, a pediatric infectious disease specialist from Tufts University, said the vaccine should be made available -- particularly for children considered to be at high risk for complications from COVID --but health officials need to present a clear picture of the relatively low risks to children of harm from the vaccines-- and from COVID.
“That has to be communicated clearly to parents so that they can participate in the decision about vaccinating a child in this age group,” Dr. Meissner said.
The results presented June 15 from studies of the shots in younger children were less impressive than those from the initial COVID vaccine trials done in adults. This was not a surprise to panelists given the rise of the omicron variant and the evolution of the pandemic, but it still led to comments about the need for further continued study of the vaccines in young children even if they are authorized.
Consider that in 2020, Pfizer won the first EUA for a COVID vaccine of any kind with data that pegged the shot’s efficacy rate at 95%. Statisticians estimated a likely possible range, or 95% confidence interval, for the vaccine efficacy rate at 90.3% to 97.6%.
Those estimates were based on finding eight cases of COVID reported among 18,198 study participants who got the Pfizer-BioNTech shot, compared with 162 cases among the 18,325 people in the placebo group, according to the FDA review of Pifzer’s initial application.
Study data
But on June 15, FDA advisers had to consider an EUA application for which the data did not make as strong a case for the vaccine’s benefit among younger patients.
Pfizer presented what the FDA called a “preliminary descriptive analysis” of vaccine efficacy among participants in Study C4591007 who received three study vaccinations, following accrual of 10 total confirmed COVID-19 cases occurring at least 7 days after the third dose.
Looking at results for study participants ages 6 to 23 months of age, there was one case in the group that got the Pfizer-BioNTech shot and two in the placebo group, pegged as a 75.6% vaccine efficacy rate -- but one with caveats to the small numbers of cases. The 95% confidence interval for this vaccine efficacy rate was reported as-369.1% to 99.6% according to the FDA staff review.
For participants 2-4 years of age with and without evidence of prior SARS-CoV-
2 infection, there were two cases in the group that got the shot and five in the placebo group showing a vaccine efficacy rate of 82.4%, with a 95% confidence interval estimated ranging between -7.6% and 98.3%. For the combined analysis of both age groups, the efficacy rate was estimated at 80.4%, with a 95% confidence interval of 14.1% and 96.7%.
Doran Fink, MD, PhD, a top official in the FDA’s vaccines division, noted that the current EUA application for expanded pediatric use involved “some very preliminary” results that involved “a small number of cases and limited follow up time.”
But he stressed that the evidence gathered to date for the Pifzer application for use of its COVID shot in infants and young children met the threshold for conditional clearance during a crisis.
“We do feel very confident that the evidentiary standard for benefit for an EUA has been met here,” but added that more data would be needed to address questions about the efficacy of the vaccine beyond a third dose and whether an additional dose may be needed.
Pfizer also used a comparison known as “immunobridging” in support of the application. This looked at SARS- CoV-2 50% neutralizing antibody titers for the children in the age group covered by the EUA application and compared them to a randomly selected subset of 16-25-year-old participants in another study,
Key data for the pending Moderna EUA for use of its shot in infants and young children came from study P204. In it, Moderna found 51 cases of COVID among 1,511 children ages 6 months to 23 months who got the vaccines, versus 34 cases among 513 children who received a placebo, according to an FDA staff review.
That resulted in a vaccine efficacy rate pegged at 50.6%, with a 95% confidence interval of 21.4% to 68.6%.
Looking at the children ages 2 to 5 years in the P204 study, there were 119 cases out of 2,594 participants who got the shot, versus 61 cases of 858 in the placebo arm, or 7.1%. That translated to a 36.8% vaccine efficacy rate, with a confidence interval 12.5% to 54.0%.
Panelist Jay Portnoy, MD, of Children’s Mercy Hospital in Kansas City said all of the pediatricians he knows are waiting for the FDA to authorize the new uses of these vaccines in infants and young children.
“The death rate from COVID in young children may not be extremely high, but it’s absolutely terrifying to parents to have their child be sick, have to go to the hospital or even go to the emergency room or their primary care doctor because they’re sick and having trouble breathing,” said Dr. Portnoy, who served as the panel’s consumer representative.
A version of this article first appeared on WebMD.com.
This article was updated on 6/16/22.
Federal advisers to the U.S. Food and Drug Administration voted unanimously June 15 to recommend the use of the Moderna and Pfizer-BioNTech COVID-19 vaccines in infants and young children.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the FDA voted 21-0 to say that benefits of a two-dose series of Moderna’s mRNA vaccine outweigh risk for use in infants and children 6 months through 5 years of age.
The panel then voted 21-0 to say that benefits of a three-dose series of the Pfizer-BioNTech mRNA vaccine outweigh risk for use in infants and children 6 months through 4 years of age.
The FDA is not bound to follow the suggestions of its advisory committees, but it often does. Moderna and Pfizer are seeking to expand emergency use authorization (EUA) for their vaccines. EUAs are special clearances used to allow use of products in connection with public health crises such as the pandemic.
The Pfizer vaccine has standard, nonemergency FDA approval for use in people 16 years of age and older. The FDA also has granted EUA clearance for use of the shot in people ages 5 to 15.
The VRBPAC on June 15 recommended granting EUA clearance for Moderna’s COVID-19 vaccine for people ages 6 to 17. The Moderna vaccine already has full approval for use in people 18 years of age and older.
Many parents have been waiting for a clearance of COVID vaccines for their infants and young children, seeking protection for them at a time of continued spread of the virus.
The White House on June 9 outlined plans for making 10 million doses of COVID vaccines available for children under the age of 5 in the coming weeks.
The Centers for Disease Control and Prevention (CDC) has scheduled a June 18 meeting of its Advisory Committee on Immunization Practices, where members of that panel will vote on recommendations about use of the Moderna and Pfizer-BioNTech vaccines in infants and young children. The last step in the approval process to get shots into arms will be endorsement by the CDC director if the committee votes in favor of the vaccines.
For and against
During the public session during the June 15 FDA meeting, speakers offered varied opinions.
Some urged the panel to vote against the EUA expansion, citing concerns about risks of COVID vaccines in general.
But at the close of the meeting, top FDA vaccine official Peter Marks, MD, PhD, urged the public to be cautious about drawing conclusions from reading incident reports of side effects.
He said he has seen a “Twitter storm” during the day about claims of side effects. but stressed that the FDA has reported to the public on the rare side effects linked to the COVID vaccines, such as myocarditis, with advisories based on a review of reports of side effects. But many of these reports, gathered from the Vaccine Adverse Event Reporting System (VAERS) system, will turn out on further inspection not to be related to vaccination.
Many other speakers urged members of the panel to support expanded use of the vaccines for infants and young children. These speakers emphasized how lack of a vaccine to date has isolated young children who remain unprotected, even with about 83% of those age 5 and older in the United States having received at least one COVID shot.
Dr. Marks noted that there have been 442 deaths from COVID among children under 4 years of age during the pandemic, a number that he compared with the 78 deaths reported in the H1N1 flu. He urged the panel “to be careful that we don’t become numb to the number of pediatric deaths because of the overwhelming number of older deaths here.”
Panelist H. Cody Meissner, MD, a pediatric infectious disease specialist from Tufts University, said the vaccine should be made available -- particularly for children considered to be at high risk for complications from COVID --but health officials need to present a clear picture of the relatively low risks to children of harm from the vaccines-- and from COVID.
“That has to be communicated clearly to parents so that they can participate in the decision about vaccinating a child in this age group,” Dr. Meissner said.
The results presented June 15 from studies of the shots in younger children were less impressive than those from the initial COVID vaccine trials done in adults. This was not a surprise to panelists given the rise of the omicron variant and the evolution of the pandemic, but it still led to comments about the need for further continued study of the vaccines in young children even if they are authorized.
Consider that in 2020, Pfizer won the first EUA for a COVID vaccine of any kind with data that pegged the shot’s efficacy rate at 95%. Statisticians estimated a likely possible range, or 95% confidence interval, for the vaccine efficacy rate at 90.3% to 97.6%.
Those estimates were based on finding eight cases of COVID reported among 18,198 study participants who got the Pfizer-BioNTech shot, compared with 162 cases among the 18,325 people in the placebo group, according to the FDA review of Pifzer’s initial application.
Study data
But on June 15, FDA advisers had to consider an EUA application for which the data did not make as strong a case for the vaccine’s benefit among younger patients.
Pfizer presented what the FDA called a “preliminary descriptive analysis” of vaccine efficacy among participants in Study C4591007 who received three study vaccinations, following accrual of 10 total confirmed COVID-19 cases occurring at least 7 days after the third dose.
Looking at results for study participants ages 6 to 23 months of age, there was one case in the group that got the Pfizer-BioNTech shot and two in the placebo group, pegged as a 75.6% vaccine efficacy rate -- but one with caveats to the small numbers of cases. The 95% confidence interval for this vaccine efficacy rate was reported as-369.1% to 99.6% according to the FDA staff review.
For participants 2-4 years of age with and without evidence of prior SARS-CoV-
2 infection, there were two cases in the group that got the shot and five in the placebo group showing a vaccine efficacy rate of 82.4%, with a 95% confidence interval estimated ranging between -7.6% and 98.3%. For the combined analysis of both age groups, the efficacy rate was estimated at 80.4%, with a 95% confidence interval of 14.1% and 96.7%.
Doran Fink, MD, PhD, a top official in the FDA’s vaccines division, noted that the current EUA application for expanded pediatric use involved “some very preliminary” results that involved “a small number of cases and limited follow up time.”
But he stressed that the evidence gathered to date for the Pifzer application for use of its COVID shot in infants and young children met the threshold for conditional clearance during a crisis.
“We do feel very confident that the evidentiary standard for benefit for an EUA has been met here,” but added that more data would be needed to address questions about the efficacy of the vaccine beyond a third dose and whether an additional dose may be needed.
Pfizer also used a comparison known as “immunobridging” in support of the application. This looked at SARS- CoV-2 50% neutralizing antibody titers for the children in the age group covered by the EUA application and compared them to a randomly selected subset of 16-25-year-old participants in another study,
Key data for the pending Moderna EUA for use of its shot in infants and young children came from study P204. In it, Moderna found 51 cases of COVID among 1,511 children ages 6 months to 23 months who got the vaccines, versus 34 cases among 513 children who received a placebo, according to an FDA staff review.
That resulted in a vaccine efficacy rate pegged at 50.6%, with a 95% confidence interval of 21.4% to 68.6%.
Looking at the children ages 2 to 5 years in the P204 study, there were 119 cases out of 2,594 participants who got the shot, versus 61 cases of 858 in the placebo arm, or 7.1%. That translated to a 36.8% vaccine efficacy rate, with a confidence interval 12.5% to 54.0%.
Panelist Jay Portnoy, MD, of Children’s Mercy Hospital in Kansas City said all of the pediatricians he knows are waiting for the FDA to authorize the new uses of these vaccines in infants and young children.
“The death rate from COVID in young children may not be extremely high, but it’s absolutely terrifying to parents to have their child be sick, have to go to the hospital or even go to the emergency room or their primary care doctor because they’re sick and having trouble breathing,” said Dr. Portnoy, who served as the panel’s consumer representative.
A version of this article first appeared on WebMD.com.
This article was updated on 6/16/22.