For decades, people at risk of anaphylaxis had essentially one choice for emergency treatment: epinephrine delivered by injection, usually via an auto-injector such as EpiPen. That changed with FDA approval of ARS Pharmaceuticals’ neffy nasal spray, the first needle-free epinephrine option for treating severe allergic reactions, but neffy is only the beginning.
A growing number of companies are developing alternatives ranging from nasal powders and sprays to a film or liquid administered under the tongue, and even a needle-free auto-injector. While none of the candidates below is FDA-approved yet, they range from early clinical development to formal FDA review.
Anaphylm — Aquestive Therapeutics
Anaphylm is a small film placed under the tongue containing dibutepinephrine, a prodrug converted to epinephrine in the body. It requires neither a needle nor a separate delivery device, potentially allowing emergency epinephrine to be carried in an exceptionally small package.
Aquestive submitted a New Drug Application (NDA), but received an FDA Complete Response Letter (CRL) in January 2026. Importantly, the agency did not question the clinical results supporting comparability with auto-injectors or identify manufacturing deficiencies. Instead, it cited human-factors concerns involving opening the pouch and correctly placing the film and requested an additional pharmacokinetic study.
Aquestive subsequently redesigned the packaging and instructions and completed the requested studies, reporting positive results in August.
Hikma Epinephrine Nasal Spray — Hikma Pharmaceuticals
Hikma is developing a single-dose liquid epinephrine nasal spray for emergency treatment of anaphylaxis.
On September 9, 2026, Hikma announced that the FDA had accepted its NDA under the 505(b)(2) pathway. Applications have also been accepted for review in Europe and the United Kingdom, with another filed in Canada.
NS002 — Nasus Pharma
NS002 takes a different nasal approach, delivering epinephrine as a dry powder. In March 2026, Nasus reported positive Phase 2 results comparing NS002 with EpiPen. NS002 reached a plasma epinephrine concentration of 100 pg/mL in a median 1.69 minutes versus 3.42 minutes for EpiPen, according to the company. No serious adverse events were reported.
Nasdepi — Belhaven Biopharma
Nasdepi is another dry-powder nasal epinephrine candidate. Belhaven is positioning it as a compact, needle-free treatment with potential advantages in temperature stability and shelf life.
The FDA accepted Belhaven’s Investigational New Drug (IND) application in October 2025, allowing the company to proceed with US clinical development.
OX640 — Orexo
OX640 is a dry-powder nasal epinephrine formulation using Orexo’s AmorphOX technology, which the company says provides strong temperature stability — an important consideration for a rescue medication carried everywhere.
OX640 has completed two clinical studies, which Orexo says demonstrated rapid epinephrine absorption and expected effects on blood pressure and heart rate, including in subjects with allergic rhinitis.
ZENEO Adrenaline — Crossject
Crossject’s ZENEO is different from the oral and nasal products. The device uses high pressure to propel liquid epinephrine through the skin and into muscle without a needle, potentially providing intramuscular delivery without a conventional auto-injector.
The ZENEO platform has undergone extensive testing and several clinical studies, and Crossject plans to pursue FDA approval through the 505(b)(2) NDA pathway.
What About UTULY?
Bryn Pharma’s UTULY is a 13.2 mg liquid epinephrine nasal spray that was previously among the more advanced needle-free candidates. Bryn completed a pivotal Phase 3 pharmacokinetic/pharmacodynamic study comparing UTULY with a 0.3 mg epinephrine auto-injector and also studied repeat dosing and nasal congestion.
That said, Bryn’s website is no longer accessible, and PitchBook lists the company as “Out of Business.”
Summary:
| Product | Developer | Delivery | Current status |
|---|---|---|---|
| Anaphylm™ | Aquestive Therapeutics | Sublingual film | NDA received FDA Complete Response Letter Jan. 2026; Q3 2026 resubmission planned |
| Hikma | Hikma Pharmaceuticals | Liquid nasal spray | NDA accepted by FDA for review Sept. 2026 |
| NS002 | Nasus Pharma | Dry-powder nasal | Phase 2 completed; pivotal study planned Q4 2026 |
| Nasdepi® | Belhaven Biopharma | Dry-powder nasal | IND accepted; pivotal biocomparability study planned |
| OX640 | Orexo | Dry-powder nasal | Two clinical studies completed; advancing toward pivotal development; seeking partner |
| IN-001 | Insignis Therapeutics | Sublingual liquid via prefilled oral syringe | Phase 1 completed; Phase 2 in preparation |
| ZENEO® | Crossject | Needle-free transcutaneous IM injection | Clinical/device development ongoing; 2028 target timeframe |
A Rapidly Changing Epinephrine Landscape
These programs show just how quickly needle-free emergency epinephrine is evolving. Patients who once had little choice beyond carrying a conventional auto-injector will eventually have a number of options, including liquid and powder nasal products, sublingual films and liquids, and needle-free injectors.
Promising clinical results are not equivalent to FDA approval, and none of these investigational products should be considered a substitute for currently prescribed, FDA-approved epinephrine. Still, more choices will eventually lead to emergency treatments that are easier to carry, easier to administer, and less intimidating to use — addressing real-world barriers that too often delay epinephrine administration during anaphylaxis. More choices will spur greater competition, resulting in lower prices.
SnackSafely will continue following these candidates as they progress through clinical development and FDA review. Stay tuned.
