Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted medicine for prophylaxis 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 FDA application was based on positive results with monthly and bi-monthly dosing in the pivotal Phase 3 OASIS-HAE and OASISplus (open label extension (OLE) and switch) studies, as well as the ongoing Phase 2 OLE study.

HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Donidalorsen is designed to reduce the production of prekallikrein (PKK), interrupting the pathway that leads to 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. "With the FDA acceptance of our donidalorsen NDA, we are poised for our second independent launch next year, assuming approval, which will allow us to continue to deliver on our goal to bring a steady cadence of medicines to patients with serious diseases."

The FDA previously granted donidalorsen Orphan Drug Designation in 2023. Otsuka, which has 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.  

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, which demonstrate that donidalorsen delivered significant and sustained reductions in HAE attacks, with overall sustained mean reduction in HAE attack rates of 96% from baseline maintained up to three years in the ongoing Phase 2 OLE study.

Across all three studies, donidalorsen was well-tolerated, with no serious treatment-emergent adverse events (TEAEs) related to donidalorsen. Most adverse events (AEs) were mild or moderate in severity, and injection site reactions were the most common AE. 

The donidalorsen ACAAI e-poster presentations can be found on Ionis' website.