FDA Rejects AdCom Recommendation for Approval of Nasal Epinephrine Spray
(Thursday, September 21, 2023)
There have been numerous controversial decisions by the FDA in recent years where it approved new drugs despite its Advisory Committees (AdCom) recommending against it. But the FDA, being an equal opportunity disagreer, at times also rejects drugs that were recommended by its AdCom for approval as was shown this week when it rejected an epinephrine nasal spray, neffy. The Neffy secured an overwhelming AdCom recommendation for approval. The company also indicated in its news release that the FDA reneged on a previous agreement with the company to not ask for additional pre-approval studies. The company is escalating the issue with the FDA Ombudsman.
AdComs serve an important role in the independent review of new drug market approval applications by providing feedback from a panel of outside experts on the quality of supporting evidence included in a given application. By their very nature, AdCom’s review is organized for applications where the FDA and the company have disagreements on the merits of the supporting evidence. Hence, the AdCom opinion is considered critical for the FDA to make its decision. AdComs review both the FDA and the company’s perspectives about the supporting data and make recommendations to the FDA about the approval or rejection of the application. In an honor system, the FDA promises to strongly “consider” the AdCom’s recommendation for the final decision regarding the application. But, by law, the FDA is not bound by its AdCom’s recommendation and can go against it. And the FDA does, when the decisions are controversial and have a high impact. This begs the question, why do we even have AdComs in the first place?
The AdCom’s have been accused of being a spectacle, a show put together by the company to sway independent reviewers, similar to how plaintiffs would try to sway a jury in a court trial. Companies have been accused of successfully manipulating the ADCom in their favor. FDA also has at times used the AdComs to showcase the controversial nature of an application and justify a questionable decision.
In this case, the FDA rejected neffy for lack of a pharmacokinetic/pharmacodynamic study assessing repeat doses of neffy compared to repeat doses of an epinephrine injection product under allergen-induced allergic rhinitis conditions. The issue was not raised at the AdCom asked to review neffy about 4 months ago. That AdCom recommended approval of neffy without the need for additional studies to demonstrate its efficacy or safety by a vote of 16 for and 6 against for use in adults and 17 for and 5 against for use in children. The company claims that 3 months after the AdCom meeting, it agreed with the FDA to revise its label and committed to a post-marketing study. The company claims it was surprised by the FDA about-turn. To be fair, at the AdCom, some members of the committee asked for additional clinical data and questioned the smaller-than-expected size of the clinical trials included in the market approval application, but they were, in the end, swayed by the company that the approval of the nasal spray was justified, hence the favorable vote.
The company is obviously unhappy. Epinephrine nasal spray is considered to be a blockbuster product. Any delay in approval results in losses of hundreds of millions of dollars for the company. So, the company has already embarked on the additional study asked for by the FDA and plans to submit the results of that study by mid-2024 and hopes for approval soon thereafter. If the Ombudsman decides in favor of the company, neffy may be in the US market much sooner.
But it leaves open the question, have the AdComs outran their utility?
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC