FDA advisers recommended that the FDA approve an intranasal epinephrine product for Type I allergic reactions, including anaphylaxis, despite concerns over the lack of clinical efficacy data.
On Thursday, members of the agency’s Pulmonary Allergy Drugs Advisory Panel said a product called ARS-1 or neffy had a favorable benefit-risk assessment as an emergency treatment for allergic reactions and anaphylaxis in both adults and children weighing 30kg. almost agreed with (~66 pounds) and the votes were 16 to 6 and 17 to 5 respectively.
The panel concluded that the surrogate endpoint data presented by the manufacturer, ARS Pharmaceuticals, are sufficient to support the efficacy of the novel non-injectable epinephrine.
“It’s been 36 years since the EpiPen and EpiPen Jr. were first approved, and no other alternative treatment route was available,” said Michael Nelson of the University of Virginia School of Medicine, Charlottesville, who voted in favor of the product. said the doctor of medicine. Both children and adults.
“I hope that this application and the conversations about it will play a role in resetting, breaking down barriers to access and use we’ve heard about today, and barriers we’ve never heard of, especially disparities in care rooted in social determinants. I wish you good health,” he continued. “Whether a drug gets approved or not, I think there is a real opportunity here to reset the playing field for everyone. hoping.”
Allergen avoidance is often used to prevent Type I allergic reactions, but epinephrine remains the first-line emergency treatment when a reaction occurs. Nevertheless, there are certain barriers to its use, such as the fear of needles and problems with correct dosing that can delay or prevent important treatments. If approved, the nasal spray under consideration would be the first needle-free form of epinephrine.
However, clinical efficacy trials were not included in the development of ARS-1, with sponsors citing feasibility and ethical concerns due to the potentially dangerous and time-sensitive nature of anaphylaxis.
“We spend our lives in clinical trials for target diseases, but here we are not studying target diseases, we are studying multiple animal surrogates, whether it is PK.” [pharmacokinetic] or PD [pharmacodynamic]”We understand why, for all good reasons, we cannot study in the setting of acute anaphylaxis,” said Dr. Leonard Baccarier of Vanderbilt University Medical Center in Nashville, Tenn. rice field.
“I think the real question is, what more can we expect reasonably and legally,” said Bascharier, who ultimately voted in favor of products for children and adults. rice field. “And if it turns out exactly the way we wanted it to, would we be able to have a lot more confidence than the situation we’re sitting in right now?”
The Advisory Panel expressed concern about this data, noting that epinephrine levels were reduced in the immediate 10 minutes after a single dose of the intranasal product in healthy patients, and that PK/PD is less sustainable. He pointed out the potential risks. Nasal congestion due to anaphylaxis.
A number of panelists suggested that post-marketing studies should be conducted if approved.
Jennifer Schwartzott, MS, the panel’s patient representative who voted in favor of nasal sprays, said, “We would like to see real post-marketing studies of efficacy and safety, but the benefits and risks are not the same.” I think it would have been enough to take into account the .
“This is a life or death unmet need. I think there was more risk in not approving than harm from the drug,” Schwarzot said. “This gives patients a choice.”
But other members questioned the unmet need and objected to trials being conducted in healthy people.
“We are getting good treatment now. [epinephrine injection] Epipens, and I think I repeat, the barriers to getting better treatment are high,” said Luis Nelson, M.D., a panelist at Rutgers New Jersey Medical School in Newark who voted against recommending approval of ARS-1. Dr., MBA said.
“While we believe there are some advantages to this alternative route of administration, we believe there are potential limitations in terms of risks and benefits,” Nelson said. “But the biggest problem I still have is that even if we believe the PK/PD data is accurate, we are still studying the data in the wrong disease and in the wrong population. I just don’t know.” Data from healthy people can be applied to anaphylactic patients. ”
The lack of precedent for approval of any form of nasal epinephrine has raised concerns among FDA reviewers. Epipens did not require submission of PK/PD data for approval decades ago, and other injectable versions of epinephrine were previously established in addition to chemical and manufacturing data, as well as human factors data. Epinephrine products had been approved using efficacy.
During the committee meeting, ARS Pharmaceuticals presented PK/PD data comparing intranasal epinephrine products to existing approved epinephrine injections. PK data for a single dose of ARS-1 were found to be within the defined range when compared to a single dose of 0.3 mg adrenaline or 0.3 mg epipen for the first 10 minutes after dosing.
ARS Pharmaceuticals also notes that the nebulizer used in its intranasal epinephrine product is the same one currently used in FDA-approved nasal spray products such as naloxone (Narcan) and diazepam (Valtoco). Did.
FDA is not required to follow advisory committee recommendations, but generally should.
