The U.S. Food and Drug Administration (FDA) has accepted for review Ionis Pharmaceuticals' New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted medicine intended for prophylactic treatment to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. The FDA has set an action date of August 21, 2025, under the Prescription Drug User Fee Act (PDUFA).
The application is supported by positive results from the pivotal Phase 3 OASIS-HAE and OASISplus studies, along with ongoing Phase 2 open-label extension (OLE) study data. These studies evaluated monthly and bi-monthly dosing regimens.
HAE is a rare genetic condition characterized by recurrent, severe swelling (angioedema) affecting various body parts, including the hands, feet, genitals, stomach, face, and throat. It is estimated to affect over 20,000 patients in the U.S. and Europe. Donidalorsen is designed to reduce the production of prekallikrein (PKK), an important mediator in the pathway leading to HAE attacks.
Clinical Efficacy and Safety
Ionis recently presented new results from the Phase 3 and Phase 2 OLE studies at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting. The data demonstrated that donidalorsen delivered significant and sustained reductions in HAE attacks. The ongoing Phase 2 OLE study showed an overall sustained mean reduction in HAE attack rates of 96% from baseline, maintained for up to three years.
Across all three studies, donidalorsen was generally well-tolerated. Most adverse events (AEs) were mild or moderate in severity, with injection site reactions being the most common AE. Notably, there were no serious treatment-emergent adverse events (TEAEs) related to donidalorsen.
Development and Regulatory Pathway
The FDA previously granted donidalorsen Orphan Drug Designation in 2023. Otsuka, which holds exclusive rights to commercialize donidalorsen in Europe and Asia Pacific, is preparing to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) this year.
"Despite currently available treatments, many people living with HAE continue to experience painful and potentially life-threatening breakthrough attacks. 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," said Brett Monia, Ph.D., chief executive officer of Ionis.
