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FDA Accepts Investigational New Drug Application for OX640 Intranasal Epinephrine Powder in Anaphylaxis
Regulatory Milestone and Clinical Background
The US Food and Drug Administration (FDA) has accepted an Investigational New Drug (IND) application for OX640, an investigational dry powder intranasal epinephrine formulation indicated for the emergency management of anaphylaxis, according to an announcement by Orexo.
Although intramuscular epinephrine administration remains the guideline-directed first-line intervention for severe systemic allergic reactions, conventional autoinjectors present substantial clinical and real-world hurdles. These include patient needle phobia, frequent device administration errors, rapid degradation requiring frequent replacement, and stringent temperature storage limits. Nikolaj Sรธrensen, MSc, president and chief executive officer of Orexo, noted that:
โAlthough epinephrine is well established as a treatment, significant challenges remain with todayโs injection-based products.โ
Formulation Characteristics, Pharmacokinetics, and Thermal Stability
OX640 is engineered using Orexoโs proprietary AmorphOX drug delivery platform. Data submitted in support of the IND application demonstrate that the formulation successfully circumvents several mechanical and logistical challenges of auto-injectable delivery. The manufacturer emphasized 4 primary therapeutic and pharmacological advantages: rapid systemic absorption, a robust pharmacokinetic (PK) exposure profile, favorable clinical tolerability, and:
โvery strong stability properties across a broad temperature range.โ
In comparative preclinical evaluations and early clinical trials, OX640 delivered plasma epinephrine exposure and bioavailability comparable to standard intramuscular autoinjectors. Furthermore, the dry powder formulation exhibited marked resistance to thermal degradation, maintaining stability for 6 months at 50 ยฐC with less than 3% active drug degradation. The formulation also demonstrated functional integrity at temperatures as low as โ20 ยฐC.
Addressing the environmental adaptability of the delivery system, Martin Jรถnsson, MSc Pharm, clinical trial manager and clinical pharmacologist at Orexo AB, previously commented:
โOur investigations suggest properties of our development nasal powder formulations that may facilitate effective use, both in winter ski slopes and on summer beaches.โ
Sรธrensen added:
โWith OX640, we have the opportunity to offer a needle-free, user-friendly, and temperature-stable product with the potential to improve treatment for patients worldwide.โ
Clinical Commentary and Future Outlook
Providing independent expert commentary, Jay A. Lieberman, MD, of the University of Tennessee Health Science Center and Le Bonheur Childrenโs Hospital, highlighted that current evidence indicates OX640 achieves systemic epinephrine concentrations comparable to standard injectable formulations.
Dr Lieberman observed that following the domestic and international approval of the first liquid intranasal epinephrine productโincluding its recent authorization in Canadaโearly clinical adoption indicates noninjectable delivery can match the efficacy of traditional autoinjectors. Dr Lieberman emphasized the clinical value of noninvasive therapeutic alternatives, noting that expanding delivery modalities (including dry powder intranasal sprays and sublingual films) may alleviate barriers to carriage, improve timely administration during an acute allergic episode, and empower shared decision-making.
The company plans to initiate the first pivotal clinical trial evaluating OX640 in the fourth quarter of 2026, with a target New Drug Application (NDA) submission planned for 2028.
Table 1. Profile and Performance Characteristics of OX640 Dry Powder Formulation vs Standard Autoinjectors
| Parameter | Standard Epinephrine Autoinjectors | OX640 Intranasal Epinephrine Powder |
| Route of Administration | Intramuscular injection | Needle-free intranasal dry powder insufflation |
| Delivery Technology | Needle-based mechanical spring device | AmorphOX proprietary drug delivery platform |
| Pharmacokinetics | Established standard plasma exposure | Comparable systemic plasma exposure profile |
| Administration Barriers | Needle aversion, device misuse, risk of injury | Needle-free, self-administrable, noninvasive |
| High-Temperature Stability | Strict ambient storage; prone to rapid thermal degradation | Stable for 6 months at 50 ยฐC (<3% degradation) |
| Low-Temperature Stability | Risk of freezing and device mechanical failure | Fully operational down to at least โ20 ยฐC |
| Intended Indication | Emergency management of Type I allergic reactions (anaphylaxis) | Emergency management of Type I allergic reactions (anaphylaxis) |
Table 2. OX640 Clinical and Regulatory Development Timeline
| Milestone | Projected / Completed Date | Status / Objective |
| FDA IND Acceptance | September 2026 | Accepted; clearance to proceed with US clinical trial program |
| First Pivotal Trial Initiation | Quarter 4, 2026 | Assessment of clinical efficacy, PK bioequivalence, and safety |
| New Drug Application (NDA) | 2028 | Formal regulatory submission seeking US FDA commercial approval |
Table 3. Contributor Affiliations and Conflict of Interest Disclosures
| Contributor | Title / Affiliation | Disclosed Competing Interests |
| Nikolaj Sรธrensen, MSc | President and Chief Executive Officer, Orexo AB | Corporate officer and leadership role at Orexo |
| Martin Jรถnsson, MSc Pharm | Clinical Pharmacologist and Clinical Trial Manager, Orexo AB | Employee and trial manager at Orexo AB |
| Jay A. Lieberman, MD | Professor/Clinician, University of Tennessee Health Science Center; Le Bonheur Childrenโs Hospital; Healio Allergy/Asthma Peer Perspective Board | Advisory/consulting roles: ARS Pharmaceuticals, Aquestive Therapeutics, DBV Technologies, Kaleo; Royalties: UpToDate |
Referencesย
- Orexo AB. FDA accepts investigational new drug application for OX640 intranasal epinephrine powder for anaphylaxis. Healio. Published September 18, 2026. Accessed September 19, 2026.
- Lieberman JA. Novel delivery routes for epinephrine in anaphylaxis: clinical implications and patient choice. Healio Allergy/Asthma Peer Perspective. Published September 18, 2026. Accessed September 19, 2026.
