Aquestive Therapeutics (NASDAQ:AQST) executives used the Citizens Life Sciences Conference to outline the company’s path forward after receiving a Complete Response Letter (CRL) from the U.S. Food and Drug Administration for Anaphylm, its oral film epinephrine product candidate for serious allergic reactions and anaphylaxis.
Chief Executive Officer Daniel Barber was joined by newly appointed Chief Medical Officer Matthew Greenhawt, a practicing allergist, and Chief Financial Officer Ernie Toth. Management emphasized that the CRL did not cite clinical deficiencies and said the remaining work is focused on human factors and additional pharmacokinetic (PK) data, with a resubmission targeted for the third quarter.
FDA CRL focused on human factors, not clinical deficiencies
According to Barber, the CRL’s deficiencies were centered on human factors—how the product is handled and administered—raised by the FDA group responsible for those reviews (DMEPA). He said the company did not have the interaction it wanted with that group during the review and that the CRL process was used to convey DMEPA’s views.
What the company plans to do next
Management said the FDA asked the company to complete two studies:
- A repeat human factors validation study, using placebo rather than active drug, which Barber described as achievable “in a very short window at a very efficient price.”
- One additional PK study, which Barber also characterized as cost-efficient and an area where the company has significant experience.
Barber said the company plans to resubmit the NDA in the third quarter. He also said a requested Type A meeting with the FDA is intended to confirm protocol details and would not slow preparations, noting that contract research organizations, protocols, and dosing dates were already being lined up.
Specific human factors issues cited in the CRL
Barber detailed three main human factors items from the CRL and the company’s intended fixes:
- Packaging opening concerns: DMEPA questioned whether the package would be difficult to open in a crisis. Barber said the company simplified the child-resistant opening mechanism by removing a “fold” step so users “now just tear.”
- Placement of the film: In the prior human factors study, Barber said 19 out of 166 participants placed the film on top of the tongue rather than under it. The company has added a picture on the pouch showing where to place the film.
- Administration/tolerability: Barber said FDA noted four individuals removed the film, though he argued removal is difficult because it turns to a gel quickly. He said the company believes adding explicit instructions such as “don’t remove the film” would address the issue, and referenced one participant who reportedly said they removed it due to disliking the mint flavor but would have kept it in during a real reaction.
Barber said success thresholds in human factors are more qualitative than traditional clinical endpoints, but added that, based on prior medical device approvals, DMEPA “seems to” look for performance “around 90%,” particularly for rescue products.
On the PK side, Barber said the company expects the FDA to seek characterization of off-label or incorrect use. He said the company is asking the FDA whether a study arm involving chewing is necessary, arguing the film dissolves in the oral cavity and ultimately ends up in the same place if swallowed. He said the company would conduct it if the FDA insists, but would remove it if not required.
Physician perspective: unmet need for needle-free epinephrine
Greenhawt framed the unmet need around adherence and readiness, arguing that patients often struggle because they don’t carry epinephrine or are reluctant to use an injector. He said delays are common, citing studies that show patients may delay treatment “anywhere from like 8 to 12 minutes,” and he cited an estimate that “something like 36%” of patients in the pre-hospital setting do not receive epinephrine before arriving for care. In his view, improving portability and ease of use could reduce delays that increase morbidity and lead to longer emergency department stays, additional epinephrine dosing, and more interventions.
Greenhawt said the medical affairs team plans to expand presence at major meetings beyond allergy, including outreach to pediatricians and advanced practice providers. He said he expects to spend the spring and summer writing “probably 10 papers or so” to disseminate existing study results and reassure prescribers about the product’s performance.
Commercial preparation, market dynamics, and cash runway
Barber said the epinephrine rescue market remains robust and growing, noting that the auto-injector market grew 5% in the fourth quarter. He also pointed to a branded nasal spray competitor investing heavily in direct-to-consumer advertising, which he said tends to broaden the overall market. Barber said it was “interesting” that the growth in auto-injector prescriptions in the fourth quarter was almost equal to the total number of nasal spray prescriptions, and he emphasized that roughly 90% of the market remains auto-injector based.
On go-to-market planning, Barber said the company has increased its focus on medical affairs, added more medical science liaisons, and expects expanded publications and conference presence. He also said the company believes a wider sales force—growing from 50 to 75—will improve physician coverage and frequency.
Asked about funding, Toth said the company ended the year with $120 million in cash. He pointed to an August capital raise led by RTW and a revenue interest financing agreement that would provide launch capital upon approval. Toth said the RTW agreement was extended through June 30, 2027, and that the company expects to end the current year with $70 million in cash, excluding any additional RTW capital.
Toth also said the company retains all rights to Anaphylm and referenced potential business development options, including possible out-licensing tied to another product, Libervant, which he said comes off ODE next year.
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.
