Ionis Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted medicine, as a prophylactic treatment for hereditary angioedema (HAE). The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2025.
The NDA submission was supported by positive data from the Phase 3 OASIS-HAE and OASISplus studies, as well as ongoing Phase 2 open-label extension (OLE) studies. These trials evaluated monthly and bi-monthly dosing regimens in adult and pediatric patients aged 12 years and older.
Addressing Unmet Needs in HAE Treatment
HAE is a rare genetic condition characterized by recurrent episodes of severe swelling in various body parts, including the hands, feet, genitals, stomach, face, and throat. Affecting an estimated 20,000 individuals in the U.S. and Europe, HAE can be life-threatening if swelling obstructs the airway.
Donidalorsen is designed to reduce the production of prekallikrein (PKK), a key protein involved in the inflammatory cascade that leads to HAE attacks. By targeting PKK, donidalorsen aims to prevent these attacks.
Clinical Trial Efficacy and Safety
Data presented at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting highlighted that donidalorsen achieved a 96% sustained mean reduction in HAE attack rates from baseline over three years in the Phase 2 OLE study. The Phase 3 trials also demonstrated significant reductions in HAE attacks.
Across the Phase 2 and Phase 3 studies, donidalorsen was generally well-tolerated. The most common adverse event was mild to moderate injection site reactions, and no serious treatment-emergent adverse events related to the drug were reported.
Future Prospects
"Despite currently available treatments, many people living with HAE continue to experience painful and potentially life-threatening breakthrough attacks," said Brett Monia, Ph.D., chief executive officer of Ionis. "Based on the totality of clinical evidence from the Phase 3 OASIS-HAE and OASISplus studies, as well as new three-year results from our Phase 2 OLE study, we believe that donidalorsen has the potential to advance the prophylactic treatment paradigm for people living with HAE."
If approved, donidalorsen will be Ionis’ second independent commercial launch. Otsuka holds exclusive rights to commercialize donidalorsen in Europe and the Asia Pacific region and is preparing to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) this year. The FDA granted donidalorsen Orphan Drug Designation in 2023.
