FDA/CDC

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

The U.S. Food and Drug Administration has unveiled a 5-year strategy aimed at improving and extending the lives of people with rare neurodegenerative diseases.

The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.

“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.

“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.

“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
 

Blueprint to ‘aggressively’ move forward

The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.

The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.

Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.

The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.

The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

A federal advisory panel on June 28 recommended updating COVID-19 booster vaccines in the United States to include an Omicron component, while urging the need for more information on how well these shots work on emerging strains of the virus.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted 19-2 in favor of a new formulation – although what that formulation will be is yet to be determined. The FDA often incorporates the views of its advisers into its decisions, although it is not bound to do so.

In this case, though, top FDA staff at the meeting seemed inclined to encourage the development of COVID vaccines modified to keep up with an evolving virus. Two Omicron subvariants, BA.4 and BA.5, which first appeared in South Africa in March 2022, have spread to the United States and have begun to increase rapidly in proportion to the virus population, the FDA said in a briefing for the meeting.

New information from the Centers for Disease Control and Prevention shows the two highly infectious subvariants now make up more than half the number of new COVID cases in the US.
 

Double-duty vaccine

In summarizing the message of the advisory committee, Peter W. Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation & Research, said panelists had lent support to modifying vaccines to protect against both the original, or “ancestral” viral strain, and against Omicron, perhaps emphasizing the newly emerging subvariants.

Dr. Marks emphasized that this is a challenging decision, as no one has a “crystal ball” to forecast how SARS-CoV-2 will evolve.

“We are trying to use every last ounce of what we can from predictive modeling and from the data that we have that’s emerging, to try to get ahead of a virus that has been very crafty,” he said.”It’s pretty darn crafty.”
 

Limited data

Voting “no” were Paul Offit, MD, of Children’s Hospital of Philadelphia and Henry Bernstein, DO, MHCM, of Hofstra/Northwell Health in New Hyde Park, N.Y.

Both Dr. Offit and Dr. Bernstein earlier in the meeting expressed doubts about the evidence gathered to date in favor of a strain change. Dr. Offit had noted that protection seems to persist from the vaccines now available.

“To date, the current prototypical vaccines, the ancestral strain vaccines do protect against serious illness,” he said. “We don’t yet have a variant that is resistant to protection against serious illness.“

Dr. Bernstein said he was “struggling” with the question as well, given the limited data gathered to date about the vaccines and emerging strains of the virus.

Other panelists also expressed reservations, while supporting the concept of altering vaccines to teach the body to fight the emerging strains as well as the original one.

Panelist Wayne Marasco, MD, PhD, of Harvard Medical School, Boston, who voted yes, noted the difficulties of keeping up with the rapidly evolving virus, saying it’s possible that Omicron strains BA.4 and BA.5 could peak within months. That could be before the vaccines are even distributed – if all goes to plan – in the fall.

“This is a step in the right direction, but we have to reevaluate this as we move forward,” Dr. Marasco said, adding that a good strategy would be to elicit antibody response to bridge more than one variant of the virus.

Even panelists like Dr. Marasco who voted yes stressed the need for further data collection about how vaccines may be adapted to a changing virus. But they also acknowledged a need to give vaccine makers a clear indication of what the medical community expects in terms of changes to these shots.

“With the waning vaccine efficacy and the confluence of risk this fall, we need to make a move sooner rather than later and direct our sponsors in the proper direction,” said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville, said before the vote.

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

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

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

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

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

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

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

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to [email protected].

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to [email protected].

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Medtronic is recalling a single lot of HeartWare Ventricular Assist Device (HVAD) System batteries because of welding defects that may cause separation of the two cell battery packs used to power the system, according to an alert on the Food and Drug Administration website.

“The welding defect may cause the battery to malfunction and no longer provide power or prevent the battery from holding a full charge or properly recharging,” the FDA said.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The agency has identified this as a class I recall, the most serious type because of the potential for serious injury or death.

Medtronic reports one death associated with this recall and two complaints in the affected lot.

Back in April, as reported by this news organization, Medtronic alerted providers that patients implanted with the Medtronic HVAD System who develop pump thrombosis could have a welding defect in the internal pump that causes the pump to malfunction.

The batteries from the recalled lot have a model number of 1650DE, were manufactured from April 13 to 19, 2021 and distributed from April 20 to July 19, 2021. The recall affects a total of 429 devices.

On May 5, 2022, Medtronic sent an urgent medical device correction notice to customers asking them to identify and quarantine all affected batteries and notify affected patients. The notice includes a patient template to help communicate directly with patients.

It also includes a customer confirmation form to initiate an exchange. The completed form should be returned to [email protected].

Medtronic is replacing the affected batteries with new product and has implemented actions to improve control of the welding process.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it’s been fraught with problems.

Earlier in June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

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.

Waldemarus/iStock/Getty Images Plus

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.

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

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.

Waldemarus/iStock/Getty Images Plus

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.

A U.S. Food and Drug Administration advisory panel has rejected the atypical antipsychotic pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of Alzheimer’s disease psychosis (ADP).

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.

Waldemarus/iStock/Getty Images Plus

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.

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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

The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).

Olivier Le Moal/Getty Images

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.

BBS affects an estimated 1,500-2,500 people in the United States.

Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.

Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.

Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.

As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.

These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.

The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
 

Safety, effectiveness in 66-week trial in 44 patients

The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.

After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.

The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.

• After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
• 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
• In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
• At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.

Setmelanotide is associated with the following warnings and precautions:

• Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
• Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
• Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
• Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.

The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

The number of pediatric hepatitis cases has remained steady since 2017, new research from the Centers for Disease Control and Prevention suggests, despite the recent investigation into children with hepatitis of unknown cause. The study also found that there was no indication of elevated rates of adenovirus type 40/41 infection in children.

But Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Children’s Hospital Los Angeles, California, says that although the study is “well-designed and robust,” that does not mean that these hepatitis cases of unknown origin are no longer a concern. He was not involved with the CDC research. “As a clinician, I’m still worried,” he said. “Why I feel like this is not conclusive is that there are other data from entities like the United Kingdom Health Security Agency that are incongruent with [these findings],” he said.

The research was published in the CDC’s Morbidity and Mortality Weekly Report.

In November 2021, the Alabama Department of Public Health began an investigation with the CDC after a cluster of children were admitted to a children’s hospital in the state with severe hepatitis, who all tested positive for adenovirus. When the United Kingdom’s Health Security Agency announced an investigation into similar cases in early April 2022, the CDC decided to expand their search nationally.

Now, as of June 15, the agency is investigating 290 cases in 41 states and U.S. territories. Worldwide, 650 cases in 33 countries have been reported, according to the most recent update by the World Health Organization on May 27, 2022. At least 38 patients have needed liver transplants, and nine deaths have been reported to WHO.

In its most recent press call on the topic, the CDC announced that it’s aware of six deaths in the United States through May 20, 2022. The COVID-19 vaccine has been ruled out as a potential cause because the majority of affected children are unvaccinated or are too young to receive the vaccine. Adenovirus infection remains a leading suspect in these sick children because the virus has been detected in 60.8% of tested cases, WHO reports.

Investigators have detected an increase in reported pediatric hepatitis cases, compared with prior years in the United Kingdom, but it was not clear whether that same pattern would be found in the United States. Neither pediatric hepatitis nor adenovirus type 40/41 are reportable conditions in the United States. In the May 20 CDC press call, Umesh Parashar, MD, chief of the CDC’s Viral Gastroenteritis Branch, said that an estimated 1,500-2,000 children aged younger than 10 are hospitalized in the United States for hepatitis every year. “That’s a fairly large number,” he said, and it might make it difficult to detect a small increase in cases.

To better estimate trends in pediatric hepatitis and adenovirus infection in the United States, investigators collected available data on emergency department (ED) visits, hospitalizations, and liver transplants associated with hepatitis in children as well as adenovirus stool testing results. Researchers used four large databases: the National Syndromic Surveillance Program; the Premier Healthcare Database Special Release; the Organ Procurement and Transplant Network; and Labcorp, which is a large commercial lab network.

To account for changes in health care utilization in the first year of the COVID-19 pandemic, the team compared hepatitis-associated ED visits, hospitalizations, and liver transplants from October 2021 to March 2022 versus the same months (January to March and October to December) in 2017, 2018, and 2019. For adenovirus stool testing, results from October 2021 to March 2022 were compared with the same calendar months (October to March) from 2017-2018, 2018-2019, and 2019-2020, to help control for seasonality.

• Weekly ED visits with hepatitis-associated discharge codes
• Hepatitis-associated monthly hospitalizations in children aged 0-4 years (22 vs. 19.5; P = .26)
• Hepatitis-associated monthly hospitalization in children aged 5-11 years (12 vs. 10.5; P = .42)
• Monthly liver transplants (5 vs. 4; P = .19)
• Percentage of stool specimens positive for adenovirus types 40/41, though the number of specimens tested was highest in March 2022

The authors acknowledged that pediatric hepatitis is rare, so it may be difficult tease out small changes in the number of cases. Also, data on hospitalizations and liver transplants have a 2- to 3-month reporting delay, so the case counts for March 2022 “might be underreported,” they wrote. Mr. Kohli noted that because hepatitis and adenovirus are not reportable conditions, the analysis relied on retrospective data from insurance companies and electronic medical records. Retrospective data are inherently limited, compared with prospective analyses, he said, and it’s possible that certain cases could be included in more than one database and thus be double-counted, whereas other cases could be missed entirely.

These findings also conflict with data from the United Kingdom, which in May reported that the average number of hepatitis cases had increased, compared with previous years, he said. More data are needed, he said, and he is involved with a study with the North American Society for Pediatric Gastroenterology and the American Association for the Study of Liver Diseases that is also collecting data to try to understand whether there has been an uptick in pediatric hepatitis cases. The study will collect patient data directly from hospitals as well as include additional pathology data, such as biopsy results.

“We should not be inhibited to look further academically – and public health–wise – while we take into cognizance this very good, robust attempt from the CDC,” he said.

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

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.

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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

The U.S. Food and Drug Administration approved baricitinib oral tablets on June 13 as the first systemic treatment for adult patients with severe alopecia areata.

The disorder with the hallmark signs of patchy baldness affects more than 300,000 people in the United States each year. In patients with the autoimmune disorder, the body attacks its own hair follicles and hair falls out, often in clumps. In February, the FDA granted priority review for baricitinib in adults with severe AA.

Baricitinib (Olumiant) is a Janus kinase (JAK) inhibitor, which blocks the activity of one or more enzymes, interfering with the pathway that leads to inflammation.

The FDA reports the most common side effects include upper respiratory tract infections, headache, acne, hyperlipidemia, increase of creatinine phosphokinase, urinary tract infection, elevated liver enzymes, inflammation of hair follicles, fatigue, lower respiratory tract infections, nausea, Candida infections, anemia, neutropenia, abdominal pain, herpes zoster (shingles), and weight gain. The labeling for baricitinib includes a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.
 

Evidence from two trials led to announcement

The decision came after review of the results from two randomized, double-blind, placebo-controlled trials (BRAVE AA-1 and BRAVE AA-2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT score) for more than 6 months.

Patients in these trials got either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary endpoint for both trials was the proportion of patients who achieved at least 80% scalp hair coverage at week 36.

In BRAVE AA-1, 22% of the 184 patients who received 2 mg of baricitinib and 35% of the 281 patients who received 4 mg of baricitinib achieved at least 80% scalp hair coverage, compared with 5% of the 189 patients in the placebo group.

In BRAVE AA-2, 17% of the 156 patients who received 2 mg of baricitinib and 32% of the 234 patients who received 4 mg achieved at least 80% scalp hair coverage, compared with 3% of the 156 patients in the placebo group.

The results were reported at the annual meeting of the American Academy of Dermatology meeting in March.

Baricitinib was originally approved in 2018 as a treatment for adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF)–blockers. It is also approved for treating COVID-19 in certain hospitalized adults. 

Two other companies, Pfizer and Concert Pharmaceuticals, have JAK inhibitors in late-stage development for AA. The drugs are already on the market for treating rheumatoid arthritis and other autoimmune diseases. FDA approval is important for insurance coverage of the drugs, which have a list price of nearly $2,500 a month, according to The New York Times.

Until now, the only treatments for moderate to severe AA approved by the FDA have been intralesional steroid injections, contact sensitization, and systemic immunosuppressants, but they have demonstrated limited efficacy, are inconvenient for patients to take, and have been unsuitable for use long term.

“Today’s approval will help fulfill a significant unmet need for patients with severe alopecia areata,” Kendall Marcus, MD, director of the Division of Dermatology and Dentistry in the FDA’s Center for Drug Evaluation and Research, said in the press release.

As Medscape reported last month, The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of baricitinib for adults with severe AA.

AA received widespread international attention earlier this year at the Academy Awards ceremony, when actor Will Smith walked from the audience up onto the stage and slapped comedian Chris Rock in the face after he directed a joke at Mr. Smith’s wife, Jada Pinkett Smith, about her shaved head. Mrs. Pinkett Smith has AA and has been public about her struggles with the disease.

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