FDA/CDC

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

The Food and Drug Administration has approved dupilumab as an add-on maintenance treatment for children aged 6 months to 5 years with moderate to severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.

The approval, announced on June 7, 2022, makes dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, the first biologic available in the United States to treat uncontrolled moderate to severe atopic dermatitis in this age group. In this age group, it is administered subcutaneously every 4 weeks. Dupilumab remains the only biologic treatment approved for patients aged 6 years and older for this indication.

Approval was based on data from a 16-week pivotal phase 3 trial that evaluated the efficacy and safety of dupilumab added to standard of care topical corticosteroids (TCS) in children aged 6 months to 5 years with uncontrolled moderate to severe atopic dermatitis. The trial’s principal investigator, Amy S. Paller, MD, professor and chair of dermatology at Northwestern University, Chicago, and colleagues, found that, at 16 weeks, 28% of patients who were treated with dupilumab, added to low-potency TCS, met the primary endpoint of clear or almost clear skin, compared with 4% of those who received low-potency TCS alone (P < .0001).

In addition, patients who received the combined treatment experienced a 70% average improvement in disease severity from baseline, compared with a 20% improvement among those in the TCS-only group (P < .0001). They also experienced a 49% improvement in itch, compared with a 2% improvement among their counterparts in the TCS-only group (P < .0001).

Outside of the United States, the study’s coprimary endpoint was achievement of 75% or greater improvement in overall disease severity. More than half of the patients who received combined treatment (53%) met this endpoint, compared with 11% in the TCS-only group (P < .0001), according to the company.

Safety results were generally consistent with the safety profile of dupilumab in atopic dermatitis for patients aged 6 years and older. The most common adverse events that were more commonly observed with dupilumab included conjunctivitis (5% vs 0% in the placebo group) and herpes viral infections (6% vs. 5% in the placebo group). Among those on dupilumab, ages 6 months to 5 years, hand,foot, and mouth disease was reported in 5% and skin papilloma were reported in 2%, but these cases did not lead to discontinuation of treatment, according to the company release.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

The Food and Drug Administration has approved adding adult patients with rheumatoid arthritis to the list of indications for the rituximab biosimilar Riabni (rituximab-arrx) on the basis of results of a randomized, double-blind, comparative clinical study with the CD20-directed cytolytic antibody reference product, Rituxan, the biosimilar’s manufacturer, Amgen, announced June 6.

The RA indication is specifically for adults with moderate to severely active disease who have had an inadequate response to one or more tumor necrosis factor inhibitors. Riabni was approved in December 2020 for the treatment of adult patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis.

The clinical study testing Riabni against Rituxan involved 311 patients with moderate to severe RA who received Riabni, Rituxan manufactured in the United States, and Rituxan manufactured in the European Union. The patients who received the U.S.-manufactured Rituxan were transitioned to receive Riabni for their second dose of rituximab, whereas patients in other groups stayed with the same treatment. The trial’s primary efficacy endpoint of the change in Disease Activity Score in 28 joints using C-reactive protein from baseline to week 24 was within the predefined equivalence margin for clinical efficacy between Riabni and Rituxan. The two products also had similar safety, pharmacokinetics, and immunogenicity profiles, according to Amgen.

Currently, Riabni and Ruxience (rituximab-pvvr) are the only two approved rituximab biosimilars in the United States. Ruxience is approved for the same indications. Rituxan alone has protected orphan drug status for the indication of adult patients with moderate to severe pemphigus vulgaris.

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

The Food and Drug Administration has approved adding adult patients with rheumatoid arthritis to the list of indications for the rituximab biosimilar Riabni (rituximab-arrx) on the basis of results of a randomized, double-blind, comparative clinical study with the CD20-directed cytolytic antibody reference product, Rituxan, the biosimilar’s manufacturer, Amgen, announced June 6.

The RA indication is specifically for adults with moderate to severely active disease who have had an inadequate response to one or more tumor necrosis factor inhibitors. Riabni was approved in December 2020 for the treatment of adult patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis.

The clinical study testing Riabni against Rituxan involved 311 patients with moderate to severe RA who received Riabni, Rituxan manufactured in the United States, and Rituxan manufactured in the European Union. The patients who received the U.S.-manufactured Rituxan were transitioned to receive Riabni for their second dose of rituximab, whereas patients in other groups stayed with the same treatment. The trial’s primary efficacy endpoint of the change in Disease Activity Score in 28 joints using C-reactive protein from baseline to week 24 was within the predefined equivalence margin for clinical efficacy between Riabni and Rituxan. The two products also had similar safety, pharmacokinetics, and immunogenicity profiles, according to Amgen.

Currently, Riabni and Ruxience (rituximab-pvvr) are the only two approved rituximab biosimilars in the United States. Ruxience is approved for the same indications. Rituxan alone has protected orphan drug status for the indication of adult patients with moderate to severe pemphigus vulgaris.

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

The Food and Drug Administration has approved adding adult patients with rheumatoid arthritis to the list of indications for the rituximab biosimilar Riabni (rituximab-arrx) on the basis of results of a randomized, double-blind, comparative clinical study with the CD20-directed cytolytic antibody reference product, Rituxan, the biosimilar’s manufacturer, Amgen, announced June 6.

The RA indication is specifically for adults with moderate to severely active disease who have had an inadequate response to one or more tumor necrosis factor inhibitors. Riabni was approved in December 2020 for the treatment of adult patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis.

The clinical study testing Riabni against Rituxan involved 311 patients with moderate to severe RA who received Riabni, Rituxan manufactured in the United States, and Rituxan manufactured in the European Union. The patients who received the U.S.-manufactured Rituxan were transitioned to receive Riabni for their second dose of rituximab, whereas patients in other groups stayed with the same treatment. The trial’s primary efficacy endpoint of the change in Disease Activity Score in 28 joints using C-reactive protein from baseline to week 24 was within the predefined equivalence margin for clinical efficacy between Riabni and Rituxan. The two products also had similar safety, pharmacokinetics, and immunogenicity profiles, according to Amgen.

Currently, Riabni and Ruxience (rituximab-pvvr) are the only two approved rituximab biosimilars in the United States. Ruxience is approved for the same indications. Rituxan alone has protected orphan drug status for the indication of adult patients with moderate to severe pemphigus vulgaris.

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The U.S. Food and Drug Administration has declined to take further action against a group of investigators at Hennepin County Medical Center/Hennepin Healthcare (HCMC) who conducted controversial studies involving ketamine and other sedatives on agitated persons without their consent.

A citizen petition filed by Public Citizen, a consumer advocacy group, had asked the FDA to initiate clinical-investigator disqualification proceedings against Jon Cole, MD, and Lauren Klein, MD, along with other researchers who participated in the studies, for “repeatedly and deliberately initiating and conducting clinical investigations of investigational drug products” without having submitted or having in effect the investigational new drug applications (INDs) required by the FDA.

In certain situations, wherein the FDA alleges that a clinical investigator has violated applicable regulations, the agency may initiate clinical investigator disqualification proceedings. The names of the disqualified researchers are then added to a federal database.

The petition, which was filed in November 2021, also requested that the FDA initiate disqualification proceedings against the institutional review board (IRB) at HCMC for repeatedly failing to comply with federal regulations that adversely affected the rights and welfare of the individuals who were enrolled in the study without their consent.

Of note, Public Citizen stated that the FDA should have required the hospital to contact the more than 1,700 patients who “were unwittingly enrolled in unethical experiments” and inform them that their rights had been violated and their health potentially endangered by the research team.

Michael A. Carome, MD, director of Public Citizen’s Health Research Group, told this news organization that it is uncommon for the FDA to disqualify researchers. “It should be more common than it is,” he said. “I think that FDA is just reluctant to take more action.”

The actions of the Hennepin investigators were “repetitive and appeared to be in deliberate violation of regulations,” he added. “The case for the FDA disqualifying the HCMC researchers is overwhelming. The FDA’s slap-on-the-wrist approach to such appalling regulatory and ethical violations risks emboldening other researchers to disregard the rights and welfare of human subjects.”

Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota, Minneapolis, agrees that the researcher from HCMC should be disqualified. “They didn’t just conduct risky, exploitative studies – they conducted them after the FDA had warned them not to proceed,” he said. “The message sent by this slap on the wrist is that investigators can do whatever they want to nonconsenting subjects, and the FDA will look the other way.”
 

Initial complaint

Public Citizen initially filed a complaint with the FDA in 2018, after learning that researchers affiliated with HCMC were conducting high-risk clinical trials involving ketamine to control agitation outside of the hospital setting. The complaint was cosigned by 64 doctors, bioethicists, and academic researchers and was also submitted to the Office for Human Research Protections.

The FDA typically allows investigational drugs to be used in emergency situation without obtaining informed consent if the therapies are known to carry a minimal risk. The IRB at HCMC had determined that this was the case with ketamine and approved the trials.

But according to Public Citizen’s complaint, prior research had suggested that ketamine could cause more complications and severe adverse events, compared with other sedatives.

The trials were conducted between 2014 and 2018, and in its letter, Public Citizen alleged that the investigators and the IRB had allowed these trials to proceed without obtaining informed consent from patients. The goal was to evaluate how well ketamine worked, compared with other drugs in calming agitated individuals: “The patients were given either ketamine or haloperidol for agitation by paramedics who responded to medical emergencies, and the goal was to see which drug worked faster,” said Dr. Carome. “Patients were only notified afterwards that they had received a sedative. Informed consent had been waived by IRB.”

In the first clinical trial conducted by HCMC, published in 2016, the researchers had hypothesized that 5 mg/kg of intramuscular ketamine would be superior to 10 mg of intramuscular haloperidol for severe prehospital agitation. Time to adequate sedation was the primary outcome measure. The study included 146 people; 64 received ketamine and 82 received haloperidol. They found that ketamine worked far more quickly than haloperidol (5 minutes vs. 17 minutes) but that the risk for complications was much higher. Complications occurred in 49% of patients receiving ketamine, compared with 5%.

“There was a 10-fold risk of adverse events,” said Dr. Carome. “And 39% of patients given ketamine had respiratory problems requiring intubation, compared to 4% who received haloperidol.”

A second study was launched in 2017, wherein ketamine was compared with midazolam in agitated patients. During the first 6-month period of the study, individuals would receive a ketamine-based protocol for prehospital agitation, and during the second 6 months, that would switch to midazolam. However, the study was halted in June 2018 after the local newspaper, the Star Tribune, reported that the city police had encouraged medical personnel to sedate agitated patients. This included individuals who had already been physically restrained.

The report stated that “in many cases, the individual being detained or arrested was not only handcuffed but strapped down on a stretcher in an ambulance before receiving ketamine,” and that it raised a “concerning question” over why these people were given the drug before they were transported to the hospital, “given the immediate effects on breathing and heart function that the drug induces.”

Along with halting the trial, HCMC asked for a review of cases involving its paramedics; an independent investigation led by former U.S. Deputy Attorney General Sally Yates was initiated to assess whether the Minneapolis police had crossed a line and urged paramedics to use ketamine.

“The decision to use ketamine was based on the study’s timeline and not on clinical judgment,” said Dr. Carome.

The FDA acknowledged receipt of the complaint and inspected the IRB records and the clinical trial data. Preliminary reports received by Public Citizen confirmed their allegations. “There were not appropriate protections for vulnerable subjects,” he said. “In 2019, the FDA did further investigations, and those reports had similar findings.”
 

FDA letters

The FDA had sent warning letters to Dr. Cole and Dr. Klein, citing them for ignoring federal safety laws in experimental research on the public. In their investigations, the FDA cited “objectionable conditions” for the studies led by Dr. Cole and Dr. Klein, according to the letters. Both researchers seemingly ignored FDA regulations and used practices that subjected patients to “significantly increased risk,” and the hospital defended its research with “factually incorrect” statements.

In a letter to Dr. Cole, the FDA noted that he never filed INDs for the trials with the FDA, as required by law, and that he also failed to write appropriate protocols to ensure that children and pregnant women were not enrolled in the research. Individuals under the influence of intoxicants also were not excluded, though the use of ketamine is cautioned in this population.

“Administration of the investigational drugs to these subjects placed them at significantly increased risk of the adverse events associated with the investigational products and decreased the acceptability of those risks,” the FDA said in its letter. “Your failure to exclude, and the lack of any precautions for, subjects under the influence of various intoxicants significantly increased the risks and/or decreased the acceptability of the risks associated with the investigational drugs.”

However, Dr. Cole conducted both studies in the prehospital setting and failed to initiate any specific measures to protect study participants, according to the FDA.
 

Petition denied

Dr. Carome noted that the researchers had committed repetitive egregious regulatory violations over a 4-year period, which were documented by the FDA in their warning letters to Dr. Cole and Dr. Klein. “We felt that they were so egregious that we need to send a signal to the community that this sort of behavior will not be tolerated,” he said. “The FDA denied our petition, and we think that sends the wrong signal to the research community.”

In their response, the FDA noted that as with judicial enforcement, “the Agency makes decisions regarding whether to pursue administrative enforcement action, including disqualification proceedings, on a case-by-case basis, considering all relevant facts and circumstances.” They added that at this time, they would not be taking further action against Dr. Cole and Dr. Klein.

“However, we intend to continue to consider all the options available to the Agency as we determine whether to pursue additional compliance actions related to this matter,” the FDA concluded.

The FDA declined to comment further on their decision.

Dr. Cole also declined to comment, but Hennepin Healthcare told this news organization that the “decision by the FDA to deny the petition validates the changes we made to strengthen and improve the clinical research program across the institution since the closing of the studies in 2018. We look forward to continuing to work with the FDA to ensure full compliance with the standards in place to protect research subjects.”

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

The FDA has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, which clears the way for approval and distribution in June.

Pfizer announced June 1 that it completed the application for a three-dose vaccine for kids between 6 months and 5 years old, and the FDA said it received the emergency use application.

Children in this age group – the last to be eligible for COVID-19 vaccines – could begin getting shots as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

Meanwhile, COVID-19 cases are still high – an average of 100,000 cases a day – but death numbers are about 90% lower than they were when President Joe Biden first took office, Dr. Jha said. 

The FDA’s advisory group, the Vaccines and Related Biological Products Advisory Committee, is scheduled to meet June 14 and June 15 to discuss data submitted by both Pfizer and Moderna.  

If the FDA gives them the green light, the CDC will then weigh in.

“We know that many, many parents are eager to vaccinate their youngest kids, and it’s important to do this right,” Dr. Jha said at a White House press briefing on June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

States can place their orders as early as June 3, Dr. Jha said, and there will initially be 10 million doses available. If the FDA gives emergency use authorization for the vaccines, the government will begin shipping doses to thousands of sites across the country.

“The good news is we have plenty of supply of Pfizer and Moderna vaccines,” Dr. Jha said. “We’ve asked states to distribute to their highest priority sites, serving the highest risk and hardest to reach areas.”

Pfizer’s clinical trials found that three doses of the vaccine for children 6 months to under 5 years were safe and effective and proved to be 80% effective against Omicron.

The FDA announced its meeting information with a conversation about the Moderna vaccine for ages 6-17 scheduled for June 14 and a conversation about the Pfizer and Moderna vaccines for young children scheduled for June 15.

Moderna applied for FDA authorization of its two-dose vaccine for children under age 6 on April 28. The company said the vaccine was 51% effective against infections with symptoms for children ages 6 months to 2 years and 37% effective for ages 2-5.

Pfizer’s 3-microgram dose is one-tenth of its adult dose. Moderna’s 25-microgram dose is one-quarter of its adult dose.

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

The Food and Drug Administration has cleared Abbot’s Freestyle Libre 3 system for use by people aged 4 years and older with diabetes.

The new system was cleared for use for both iOS- and Android-compatible mobile apps, enabling real-time glucose readings in contrast to the “intermittently scanned” capability of prior Libre versions. The Libre 3 allows for optional alarms and notifications of urgent low or high glucose levels, as well as remote monitoring by health care professionals or the patient’s family members and/or friends.

The FreeStyle Libre 3 was granted a CE Mark in Europe in October 2020.

Smaller, thinner, and better integration

According to Abbott, the Libre 3 is the first continuous glucose monitoring (CGM) system to show a mean absolute relative difference (MARD) of less than 8% compared with a gold-standard glucose measure. The average Libre 3 MARD is 7.9%, compared with 9.3% for the Libre 2. The Libre 3 is also the “smallest and thinnest” CGM, roughly the size of two stacked U.S. pennies, worn on the upper arm.

And, the company said, the Libre 3 has a Bluetooth integration of up to 33 feet, a range 50% further than other CGMs.   

This version follows the FreeStyle Libre 2, approved in June 2020, and its compatible iPhone app, approved in August 2021.

The Libre 3 will be priced the same as the Libre 2, at about one-third the cost of other CGM systems. However, it is not currently eligible for Medicare reimbursement. Medicaid eligibility may vary by state.

“I applaud Abbott for making their CGM system the most affordable and addressing disparities in care so patients living with diabetes can avoid complications and optimize their quality of life,” Eugene E. Wright Jr., MD, of Duke University, Durham, N.C., said in an Abbott statement.

“I have seen real-world evidence that diabetes technologies like CGMs have helped my patients safely achieve improved glycemic control,” he said.

The FreeStyle Libre 3 sensor will be available at participating pharmacies later this year.

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

The Food and Drug Administration has cleared Abbot’s Freestyle Libre 3 system for use by people aged 4 years and older with diabetes.

The new system was cleared for use for both iOS- and Android-compatible mobile apps, enabling real-time glucose readings in contrast to the “intermittently scanned” capability of prior Libre versions. The Libre 3 allows for optional alarms and notifications of urgent low or high glucose levels, as well as remote monitoring by health care professionals or the patient’s family members and/or friends.

The FreeStyle Libre 3 was granted a CE Mark in Europe in October 2020.

Smaller, thinner, and better integration

According to Abbott, the Libre 3 is the first continuous glucose monitoring (CGM) system to show a mean absolute relative difference (MARD) of less than 8% compared with a gold-standard glucose measure. The average Libre 3 MARD is 7.9%, compared with 9.3% for the Libre 2. The Libre 3 is also the “smallest and thinnest” CGM, roughly the size of two stacked U.S. pennies, worn on the upper arm.

And, the company said, the Libre 3 has a Bluetooth integration of up to 33 feet, a range 50% further than other CGMs.   

This version follows the FreeStyle Libre 2, approved in June 2020, and its compatible iPhone app, approved in August 2021.

The Libre 3 will be priced the same as the Libre 2, at about one-third the cost of other CGM systems. However, it is not currently eligible for Medicare reimbursement. Medicaid eligibility may vary by state.

“I applaud Abbott for making their CGM system the most affordable and addressing disparities in care so patients living with diabetes can avoid complications and optimize their quality of life,” Eugene E. Wright Jr., MD, of Duke University, Durham, N.C., said in an Abbott statement.

“I have seen real-world evidence that diabetes technologies like CGMs have helped my patients safely achieve improved glycemic control,” he said.

The FreeStyle Libre 3 sensor will be available at participating pharmacies later this year.

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

The Food and Drug Administration has cleared Abbot’s Freestyle Libre 3 system for use by people aged 4 years and older with diabetes.

The new system was cleared for use for both iOS- and Android-compatible mobile apps, enabling real-time glucose readings in contrast to the “intermittently scanned” capability of prior Libre versions. The Libre 3 allows for optional alarms and notifications of urgent low or high glucose levels, as well as remote monitoring by health care professionals or the patient’s family members and/or friends.

The FreeStyle Libre 3 was granted a CE Mark in Europe in October 2020.

Smaller, thinner, and better integration

According to Abbott, the Libre 3 is the first continuous glucose monitoring (CGM) system to show a mean absolute relative difference (MARD) of less than 8% compared with a gold-standard glucose measure. The average Libre 3 MARD is 7.9%, compared with 9.3% for the Libre 2. The Libre 3 is also the “smallest and thinnest” CGM, roughly the size of two stacked U.S. pennies, worn on the upper arm.

And, the company said, the Libre 3 has a Bluetooth integration of up to 33 feet, a range 50% further than other CGMs.   

This version follows the FreeStyle Libre 2, approved in June 2020, and its compatible iPhone app, approved in August 2021.

The Libre 3 will be priced the same as the Libre 2, at about one-third the cost of other CGM systems. However, it is not currently eligible for Medicare reimbursement. Medicaid eligibility may vary by state.

“I applaud Abbott for making their CGM system the most affordable and addressing disparities in care so patients living with diabetes can avoid complications and optimize their quality of life,” Eugene E. Wright Jr., MD, of Duke University, Durham, N.C., said in an Abbott statement.

“I have seen real-world evidence that diabetes technologies like CGMs have helped my patients safely achieve improved glycemic control,” he said.

The FreeStyle Libre 3 sensor will be available at participating pharmacies later this year.

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

The U.S. Food and Drug Administration has approved a label extension for oral risdiplam (Evrysdi, Genentech) to include presymptomatic infants younger than 2 months old with spinal muscular atrophy (SMA).

As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.

The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.

After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.

Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.

All babies were alive at 12 months without permanent ventilation.

“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.

“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
 

From newborns to older adults?

SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.

SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.

Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.

As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.

“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release. 

“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.

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

The U.S. Food and Drug Administration has approved a label extension for oral risdiplam (Evrysdi, Genentech) to include presymptomatic infants younger than 2 months old with spinal muscular atrophy (SMA).

As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.

The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.

After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.

Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.

All babies were alive at 12 months without permanent ventilation.

“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.

“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
 

From newborns to older adults?

SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.

SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.

Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.

As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.

“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release. 

“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.

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

The U.S. Food and Drug Administration has approved a label extension for oral risdiplam (Evrysdi, Genentech) to include presymptomatic infants younger than 2 months old with spinal muscular atrophy (SMA).

As previously reported, the FDA first approved oral risdiplam for SMA in children older than age 2 years in 2020.

The FDA expanded the indication for risdiplam to include babies younger than 2 months old because of interim safety and efficacy data from the ongoing RAINBOWFISH study. It includes 25 babies from birth to 6 weeks of age at first dose, all of whom have genetically diagnosed SMA but are not yet presenting with symptoms.

After 12 months of risdiplam treatment, the majority of presymptomatic infants with SMA reached key motor milestones, Genentech said in a news release.

Of the six babies with two or three copies of the SMN2 gene, all were able to sit after 1 year of active treatment, roughly two-thirds could stand, and half could walk independently.

All babies were alive at 12 months without permanent ventilation.

“The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” Richard Finkel, MD, principal investigator of the trial, said in the release.

“With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed,” added Dr. Finkel, who is director of the experimental neuroscience program, St. Jude Children’s Research Hospital, Memphis.
 

From newborns to older adults?

SMA is a rare and often fatal genetic disease that causes muscle weakness and progressive loss of movement.

SMA, which affects about 1 in 10,000 babies, is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein, which is critical for the maintenance and function of motor neurons.

Risdiplam is an orally administered, centrally and peripherally distributed small molecule that modulates survival motor neuron 2 (SMN2) premessenger RNA splicing to increase SMN protein levels.

As part of the label extension, the prescribing information for risdiplam has also been updated to include 2-year pooled data from parts 1 and 2 of the FIREFISH study, which demonstrated long-term efficacy and safety in symptomatic infants with Type 1 SMA, the company noted.

“Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA, from presymptomatic newborns to older adults,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in the release. 

“We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers,” Dr. Garraway added.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

The anticipated U.S. Food and Drug Administration approval of VP-102 for the treatment of molluscum contagiosum has been delayed because of deficiencies identified at a contract manufacturing organization, according to Verrica Pharmaceuticals, which is developing the product.

VP-102 is a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

According to a press release from Verrica, the only deficiency listed in the FDA’s complete response letter stemmed from a general reinspection of Sterling Pharmaceuticals Services, which manufactures Verrica’s bulk solution drug product. Although none of the issues identified by the FDA during the reinspection were specific to the manufacturing of VP-102, FDA policy prevents approval of a new drug application when a contract manufacturing organization has an unresolved classification status or is placed on “official action indicated” status.

According to the press release, Verrica will “continue to work collaboratively” with the FDA to bring VP-102 to the market as soon as possible. The company has completed phase 2 studies of VP-102 for the treatment of common warts and for the treatment of external genital warts, the release said.

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

The anticipated U.S. Food and Drug Administration approval of VP-102 for the treatment of molluscum contagiosum has been delayed because of deficiencies identified at a contract manufacturing organization, according to Verrica Pharmaceuticals, which is developing the product.

VP-102 is a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

According to a press release from Verrica, the only deficiency listed in the FDA’s complete response letter stemmed from a general reinspection of Sterling Pharmaceuticals Services, which manufactures Verrica’s bulk solution drug product. Although none of the issues identified by the FDA during the reinspection were specific to the manufacturing of VP-102, FDA policy prevents approval of a new drug application when a contract manufacturing organization has an unresolved classification status or is placed on “official action indicated” status.

According to the press release, Verrica will “continue to work collaboratively” with the FDA to bring VP-102 to the market as soon as possible. The company has completed phase 2 studies of VP-102 for the treatment of common warts and for the treatment of external genital warts, the release said.

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

The anticipated U.S. Food and Drug Administration approval of VP-102 for the treatment of molluscum contagiosum has been delayed because of deficiencies identified at a contract manufacturing organization, according to Verrica Pharmaceuticals, which is developing the product.

VP-102 is a proprietary drug-device combination of cantharidin 0.7% administered through a single-use precision applicator, which has been evaluated in phase 3 studies of patients with molluscum aged 2 years and older. It features a visualization agent so the person applying the drug can see which lesions have been treated. It also contains a bittering agent to mitigate oral ingestion by children.

According to a press release from Verrica, the only deficiency listed in the FDA’s complete response letter stemmed from a general reinspection of Sterling Pharmaceuticals Services, which manufactures Verrica’s bulk solution drug product. Although none of the issues identified by the FDA during the reinspection were specific to the manufacturing of VP-102, FDA policy prevents approval of a new drug application when a contract manufacturing organization has an unresolved classification status or is placed on “official action indicated” status.

According to the press release, Verrica will “continue to work collaboratively” with the FDA to bring VP-102 to the market as soon as possible. The company has completed phase 2 studies of VP-102 for the treatment of common warts and for the treatment of external genital warts, the release said.

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