FDA Accepts Ionis' New Drug Application for Donidalorsen for HAE Prevention

Ionis Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for review, pertaining to donidalorsen, an RNA-targeted medicine aimed at preventing attacks of hereditary angioedema (HAE). The FDA has scheduled an action date for August 21, 2025, under the Prescription Drug User Fee Act (PDUFA).

Donidalorsen is designed to reduce the production of prekallikrein (PKK), consequently interrupting the pathway that leads to HAE attacks. HAE is a rare genetic condition characterized by recurrent episodes of severe swelling in various parts of the body, such as the hands, feet, genitals, stomach, face, and throat. This condition is potentially life-threatening.

The FDA’s acceptance of the NDA is based on positive results from the Phase 3 OASIS-HAE and OASISplus studies, along with data from an ongoing Phase 2 OLE study. These studies demonstrated significant and sustained reductions in HAE attack rates, with overall sustained mean reduction rates of 96% from baseline, maintained up to three years in the Phase 2 OLE study. Donidalorsen was well-tolerated across all studies, with no serious treatment-emergent adverse events related to the drug. Most adverse events were mild or moderate, with injection site reactions being the most common.

Brett Monia, Ph.D., CEO of Ionis, expressed optimism about donidalorsen's potential to advance the treatment of HAE. He stated that despite existing treatments, many HAE patients continue to suffer from breakthrough attacks. The clinical evidence suggests that donidalorsen could significantly improve prophylactic treatment for these individuals.

In 2023, the FDA granted donidalorsen Orphan Drug Designation. 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. Recently, Ionis 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. These findings reinforced the drug’s efficacy and safety profile.

Hereditary angioedema (HAE) affects over 20,000 people in the U.S. and Europe. In the U.S., doctors often use prophylactic treatments to minimize the frequency and severity of HAE attacks. Donidalorsen offers a promising new option for these preventative treatments by targeting PKK, a protein involved in activating inflammatory mediators that lead to HAE attacks.

Ionis Pharmaceuticals has a history of developing innovative RNA-targeted medicines. Over three decades, the company has created medicines that address serious diseases, with five marketed products and a robust pipeline focusing on areas like neurology and cardiology. Ionis is committed to advancing RNA therapies and exploring new gene-editing techniques, driven by a deep understanding of disease biology and cutting-edge technology. The goal is to bring life-changing treatments to patients in need.