Ionis Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted for review its New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted medicine for the prophylactic treatment to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2025.
The application is supported by positive results from the Phase 3 OASIS-HAE and OASISplus studies, along with data from an ongoing Phase 2 open-label extension (OLE) study. These studies evaluated monthly and bi-monthly dosing regimens.
Clinical Evidence
Data presented at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting highlighted that donidalorsen delivered significant and sustained reductions in HAE attacks. The ongoing Phase 2 OLE study demonstrated an overall sustained mean reduction in HAE attack rates of 96% from baseline, maintained for up to three years.
Across the Phase 3 and Phase 2 OLE studies, donidalorsen was generally well-tolerated. Most adverse events were mild to moderate in severity, with injection site reactions being the most common.
Donidalorsen's Mechanism of Action
Donidalorsen is designed to reduce the production of prekallikrein (PKK), a key component in the pathway that leads to HAE attacks. By targeting PKK, donidalorsen aims to prevent the acute swelling episodes characteristic of HAE.
Market and Regulatory Landscape
The FDA granted donidalorsen Orphan Drug Designation in 2023. Otsuka holds exclusive rights to commercialize donidalorsen in Europe and Asia Pacific and is preparing to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) this year.
Hereditary Angioedema (HAE)
HAE is a rare, genetic condition characterized by recurrent episodes of severe swelling (angioedema) affecting various body parts, including the hands, feet, genitals, stomach, face, and throat. It is estimated to affect more than 20,000 patients in the U.S. and Europe. Prophylactic treatment approaches are frequently used to prevent and reduce the severity of HAE attacks.
"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.
