Executives from Aquestive Therapeutics (NASDAQ:AQST) said the U.S. Food and Drug Administration has issued a complete response letter (CRL) for the company’s New Drug Application for Anaphylm, an epinephrine sublingual film being developed for the treatment of anaphylaxis, requiring additional work before the agency will approve the product for marketing.
On the company’s conference call, Chief Executive Officer Dan Barber described the CRL as “unfortunate and seemingly unnecessary,” but characterized it as a “major de-risking event” because, he said, the FDA cited no deficiencies related to pharmacokinetics (PK) bracketing, repeat-dose safety, or the “sustainability of Anaphylm’s performance.” Barber also said the CRL contained no chemistry, manufacturing, and controls (CMC) comments.
FDA feedback centered on human factors
According to the company, the FDA’s Division of Medication Error Prevention and Analysis (DMEPA) raised several concerns, including:
- Pouch opening and potential tearing of the film: In the human factors validation study, Barber said one participant—a child—did not open a pouch, noting the company currently uses a child-resistant pouch. He also said there were six instances of participants tearing a film while opening, though all resulted in full dosing.
- Administration concerns, including chewing: Barber said four out of 166 participants were recorded as chewing the film; of those four, only one had received the instructions for use prior to dosing. He said reviewing study videos suggested participants did not read the instructions on the pouch.
- Tolerability and potential premature removal: DMEPA cited tingling, burning, and taste as potential issues. Barber said the company saw zero instances of film removal across 11 clinical studies, including in pediatrics. In the human factors validation study, he said four participants removed the film, citing taste (two) or a burning sensation (two), not tingling.
Barber said the company has “previewed a revised opening mechanism” with the FDA and believes the alternate opening will address the agency’s concerns. He also said that adding pictures to the pouch could improve administration for users who do not read the written instructions.
Additional studies required before resubmission
Management said there are two key items needed prior to resubmission: a new human factors validation study and an additional PK study related to film placement and administration.
In response to analyst questions, the company said the human factors study would generally align with FDA guidance, with Senior Vice President of Regulatory Melina Cioffi stating expectations are typically about 15 participants per arm, or roughly 75 participants overall.
Chief Development Officer Matthew Davis said the FDA “very clearly mapped out” the PK study design the agency wants, including evaluation of chewing with and without swallowing, alternate administration sites, and self-administration informed by the human factors work. Davis said the FDA also requested an injectable comparator and included an element involving placement of the film by a healthcare practitioner. He said the company is considering either a parallel or sequential design.
Barber said the FDA is not requiring a repeat-dose PK study and that the company does not currently see a need to conduct one.
Resubmission timing, review clock, and approval expectations
Barber said the company expects a “straightforward path to resubmission” and anticipates resubmitting in the third quarter of this year. He also said the company plans to seek rapid review and approval once the resubmission is filed.
Management indicated that the resubmission would likely carry a six-month review timeline, while noting that a competing product in the category had a six-month clock but was approved in four months. Barber said the “longest clock is six months.”
Interim Chief Medical Officer Gary Slatko said the CRL “defines a clear path” and that the agency’s feedback removes many uncertainties, adding that some uncertainties can be addressed through labeling.
Commercial preparation and ex-U.S. plans
Chief Commercial Officer Sherry Korczynski said the epinephrine market continues to be dominated by autoinjectors and that she expects that to remain the case in 2026. She said the company’s commercial investments in 2025 remain relevant to the updated timeline and that the company will be “commercial-ready.” Korczynski also said the company was not planning to hire its sales force until approval, though it had identified district sales managers and sales representatives it expects to revisit closer to an approval date.
Korczynski highlighted recent market research conducted over the last three to four months, saying that when patients could “see, feel, [and] touch” Anaphylm and compare it with other products, patients chose Anaphylm 96% of the time.
On international strategy, Barber said the company plans to proceed with ex-U.S. filings and anticipates filing in Canada and Europe this year, with distribution strategy and potential partnerships becoming a priority. Cioffi said the company has had pre-submission meetings with Canadian and European regulators and described a “clear path forward,” and added that an upcoming meeting with the U.K.’s MHRA will help inform the regulatory path in the United Kingdom.
In closing remarks, Barber reiterated the company’s confidence in the program’s importance to patients and said the company believes it is now “much closer to approval” than it was before receiving the FDA’s response.
About Aquestive Therapeutics (NASDAQ:AQST)
Aquestive Therapeutics, Inc is a specialty pharmaceutical company focused on the development and commercialization of novel drug delivery systems. Leveraging its proprietary PharmFilm® technology, Aquestive designs thin-film formulations that facilitate sublingual, buccal and oral delivery of small molecules, offering rapid onset of action and improved patient compliance compared with traditional dosage forms.
The company’s lead product, Libervant® (diazepam) Buccal Film, is approved by the U.S.
