After 35 Years of Injection-Only Options, Needle-Free Epinephrine Expands Globally While U.S. Approval Faces Packaging Redesign
February 2nd, 2026: FDA Issues Complete Response Letter for AnaphylmNew here? Follow stories to track developments over time. Create a free account to get updates when stories you care about change.
For nearly four decades, Americans facing life-threatening allergic reactions had exactly one option: stab themselves with a needle. The EpiPen and its competitors delivered epinephrine effectively, but needle phobia kept roughly 30% of patients from using their prescribed devices during emergencies—contributing to preventable deaths. Now the needle era is ending. The Food and Drug Administration (FDA) approved the first needle-free alternative, a nasal spray called neffy, in August 2024. On February 2, 2026, the FDA issued a Complete Response Letter for Anaphylm, a dissolvable film placed under the tongue, rejecting the application but limiting deficiencies to human factors and packaging rather than safety or efficacy concerns. Aquestive Therapeutics expects to resubmit in the third quarter of 2026 after conducting a redesigned human factors validation study and a supporting pharmacokinetics study.
The stakes extend beyond convenience. An estimated 33 million Americans carry severe allergy risks, with food allergies alone triggering 30,000 emergency room visits and 150 to 200 deaths annually. Delayed epinephrine use is a leading risk factor in fatal reactions. Meanwhile, neffy is expanding internationally—the European Commission approved EURneffy in August 2024, and in February 2026, the European Medicines Agency's Committee for Medicinal Products for Human Use issued a positive opinion for neffy in children. If Anaphylm gains approval following its resubmission and both needle-free options gain market traction, the treatment gap created by fear of needles could narrow substantially—potentially saving lives that current delivery methods cannot reach.
What is neffy® (epinephrine nasal spray)?
neffy® (epinephrine nasal spray) for Anaphylaxis
Plastic single use syringe injectors of different sizes with dose of vaccine placed on bright yellow surface without needle protective cover
Needle-free epinephrine was developed in San Diego
CBS 8 San Diego
FDA just approved this needle-free EpiPen alternative
5NEWS
1 Year Since the FDA Approved Epinephrine Nasal Spray
HCPLive
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New Jersey-based pharmaceutical company specializing in oral film drug delivery technology.
San Diego-based pharmaceutical company that developed neffy, the first needle-free epinephrine treatment.
US federal agency responsible for approving drugs and medical devices for market.
The FDA rejected Anaphylm's NDA but limited deficiencies to human factors and packaging—not safety or efficacy. Aquestive must redesign the pouch opening mechanism and conduct a new human factors validation study plus a supporting pharmacokinetics study. Company expects to resubmit in Q3 2026.
The European Medicines Agency's Committee for Medicinal Products for Human Use issued a positive opinion for EURneffy (neffy) for emergency treatment of anaphylaxis in children, expanding needle-free access in Europe.
The PDUFA target action date for Anaphylm. The FDA may approve, reject, or request additional information.
The FDA identified unspecified deficiencies in the Anaphylm application that prevent labeling discussions, though the review continues.
ARS Pharmaceuticals filed a citizen petition urging the FDA to delay approval of Anaphylm, citing safety, dosing, and real-world use concerns about the sublingual epinephrine film.
The FDA accepted Aquestive's application and assigned a January 31, 2026 target action date. No advisory committee meeting required.
Aquestive submitted its New Drug Application for Anaphylm sublingual film, supported by 11 clinical studies with 967 administrations.
The FDA approved a 1mg neffy dose for children ages 4 and older weighing 33-66 pounds, expanding needle-free access.
The FDA approved neffy nasal spray for adults and children over 66 pounds—the first needle-free epinephrine option in 35 years.
A generic version of the EpiPen became available, offering a lower-cost needle-based option at $150-200.
Heather Bresch testified before Congress about EpiPen price increases from $100 to over $600. The scandal intensified calls for alternatives.
Sanofi voluntarily recalled all Auvi-Q auto-injectors due to potential dosage delivery failures, temporarily leaving EpiPen as the dominant option.
The FDA approved Auvi-Q, an auto-injector with voice guidance developed by twin brothers with severe allergies. It remained needle-based.
Mylan acquired US marketing rights to EpiPen from Merck KGaA. The company would raise prices from roughly $100 to over $600 by 2016.
The FDA approved the first modern epinephrine auto-injector, establishing needle-based delivery as the standard of care for anaphylaxis treatment.
Discussed by: HCPLive, Allergic Living, and industry analysts covering the January 2026 PDUFA date
The FDA approves Anaphylm despite the identified deficiencies, determining they can be addressed through labeling or post-marketing commitments. Aquestive launches the sublingual film in 2026, giving patients two needle-free options: nasal spray and oral film. Competition between neffy and Anaphylm could drive down prices and accelerate adoption of needle-free delivery.
Discussed by: Fierce Biotech, Patient Care Online, and pharmaceutical industry analysts
The January 9 deficiency notification signals deeper issues than expected. The FDA issues a Complete Response Letter requiring additional clinical data, manufacturing changes, or labeling revisions. Approval slips to late 2026 or 2027, leaving neffy as the sole needle-free option and reducing competitive pressure on pricing.
Discussed by: Yale Medicine, allergy specialists noting neffy's contraindications
Both products reach market, but their different delivery methods create distinct patient populations. Neffy's warnings about nasal polyps and nasal surgery push some patients toward Anaphylm's sublingual film. The oral film captures patients who cannot use nasal spray, while neffy retains those comfortable with nasal delivery.
Discussed by: GoodRx, Consumer Reports, and patient advocacy groups
Even with FDA approval, high list prices and limited insurance coverage keep needle-free options out of reach for many patients. Generic EpiPen alternatives at $150-200 remain the default choice for cost-conscious consumers, and needle-free adoption remains concentrated among patients with documented needle phobia or ability to pay out of pocket.
Discussed by: Industry analysts, Seeking Alpha contributors following AQST stock
The FDA's January 9 deficiency notification delays Anaphylm approval into late 2026 or 2027, giving neffy 12-18 additional months as the sole needle-free option. ARS Pharmaceuticals uses this time to establish market dominance, secure preferred formulary positions with insurers, and build brand recognition. By the time Anaphylm launches, neffy has already captured significant market share and established physician prescribing patterns that prove difficult to disrupt.
Discussed by: Aquestive management, pharmaceutical analysts tracking AQST stock
Aquestive successfully completes human factors and pharmacokinetics studies by Q3 2026 and resubmits the NDA. The FDA grants approval in Q4 2026, bringing Anaphylm to market alongside neffy. Both products establish distinct market positions—neffy for nasal delivery, Anaphylm for sublingual administration—reducing reliance on needle-based epinephrine and creating competitive pricing pressure.
Discussed by: Aquestive investor relations, European regulatory analysts
Anaphylm receives European marketing authorization in late 2026 before U.S. approval, allowing Aquestive to establish commercial presence and clinical experience in Europe. This international success strengthens the company's position for eventual U.S. launch and demonstrates product viability to U.S. physicians and payers.
Mylan raised the price of EpiPen two-packs from roughly $100 in 2007 to over $600 by 2016—a 500% increase. The company's chief executive, Heather Bresch, testified before Congress and claimed Mylan made only $50 profit per pen. Public outrage intensified as families reported rationing doses and schools struggled to afford devices.
Mylan launched an authorized generic at $300. State and federal investigations followed. Bresch faced intense criticism for her $19 million salary.
The scandal became a symbol of pharmaceutical pricing problems and accelerated interest in alternatives. Mylan eventually agreed to a $264 million class-action settlement in 2022.
The pricing crisis demonstrated market dysfunction when a single delivery method dominates. Needle-free alternatives create competition that could prevent future monopoly pricing.
Sanofi recalled all Auvi-Q auto-injectors after reports of potential dosage delivery failures. The recall removed EpiPen's main competitor from the market just before the pricing scandal erupted. Kaléo later reacquired the product and relaunched it in 2017 with an automated robotic production line.
EpiPen's market share temporarily exceeded 89%. Patients with Auvi-Q prescriptions scrambled to switch devices.
The recall showed how thin the competitive field was and how vulnerable patients were to a single-product market.
The recall highlighted the risks of limited treatment options. Multiple needle-free alternatives would create redundancy that protects patients from supply disruptions.
The FDA approved Suboxone sublingual film for opioid dependence treatment, using the same PharmFilm technology Aquestive is now applying to epinephrine. The film offered a discreet, convenient alternative to tablets and became one of the most successful sublingual film products.
Suboxone Film gained rapid market acceptance, eventually capturing most of the buprenorphine market.
The product validated sublingual film delivery for medications requiring rapid absorption and demonstrated the commercial potential of the technology platform.
Aquestive's PharmFilm technology has a proven track record with FDA approval and commercial success. Anaphylm uses the same underlying platform.