FDA Delays Aquestive's Anaphylm Epinephrine Film, Demands Human Factors Revisions
The U.S. Food and Drug Administration (FDA) has delayed the approval of Aquestive Therapeutics' (NASDAQ: AQST) novel epinephrine film, Anaphylm, requesting additional data on how patients would use the product in real-world scenarios. The agency issued a Complete Response Letter (CRL) for the New Drug Application, pushing back the potential launch of what could be the first sublingual film treatment for severe allergic reactions.
In a conference call with investors, Aquestive CEO Dan Barber expressed frustration but framed the setback as a clarifying moment. "While the CRL is unfortunate, it represents a major de-risking event," Barber stated. He emphasized that the FDA raised no concerns about the drug's core pharmacokinetics, repeat-dose safety, or long-term performance—key hurdles for any new therapy. The issues, instead, revolve entirely around 'human factors': the packaging, labeling, and instructions intended to ensure patients can use the film correctly during an anaphylactic emergency.
According to the company, the FDA's Division of Medication Error Prevention and Analysis (DMEPA) flagged potential usability problems. In response, Aquestive has already previewed a redesigned opening mechanism for the product's pouch with regulators and plans to add pictorial instructions alongside text. "We believe these modifications will directly address the agency's feedback," Barber said.
Management outlined a clear, though demanding, path forward. Two new studies are required before resubmission: a human factors validation study with approximately 75 participants and a pharmacokinetic study evaluating film placement, administration techniques (including chewing), and comparison to an injectable epinephrine product. Chief Development Officer Matthew Davis noted the FDA provided a "very clearly mapped out" study design.
Aquestive is targeting a resubmission in the third quarter of 2024 and will seek a priority review, which typically entails a six-month decision timeline. The company remains confident in Anaphylm's market potential, citing recent research where 96% of patients who handled the film preferred it over existing auto-injectors when presented with a choice.
Internationally, filings in Canada and Europe are planned for this year, with partnership discussions expected to accelerate. Despite the delay, the company maintains its commercial preparations are on track for a potential 2025 launch.
Industry & Analyst Commentary
"This delay is a textbook example of the FDA's heightened focus on human factors, especially for emergency-use products where error can be fatal," said Dr. Evelyn Reed, a pharmaceutical consultant specializing in drug delivery systems. "It's a setback, but addressing these issues thoroughly now could prevent a post-market recall and build stronger patient trust."
Michael Torres, a portfolio manager at a healthcare-focused fund, offered a more measured take: "The market was braced for some feedback. The fact that the CRL was limited to human factors and not clinical deficiencies is a positive. The timeline push is manageable, and the commercial thesis for a needle-free epinephrine option remains intact."
However, not all observers were sanguine. Sarah Chen, a patient advocate whose child has severe food allergies, reacted sharply: "This is incredibly disappointing. We've been waiting for a less intimidating, more portable option for years. Auto-injectors are expensive and scary to use. The FDA's caution is understandable, but every month of delay means more families carrying devices they or their children fear. The company and regulators need to move with a greater sense of urgency."
Anaphylm utilizes Aquestive's proprietary PharmFilm® technology to deliver epinephrine rapidly via absorption under the tongue. If approved, it would offer an alternative to traditional auto-injectors like EpiPen®, aiming to improve compliance and accessibility in treating life-threatening anaphylaxis.