Ionis Pharmaceuticals' donidalorsen, an investigational RNA-targeted prophylactic medicine, is showing promise in preventing attacks of hereditary angioedema (HAE). New data presented at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) / World Allergy Organization (WAO) Joint Congress highlight sustained HAE attack rate reduction and improved disease control.
The New Drug Application (NDA) for donidalorsen is currently under review by the U.S. Food and Drug Administration (FDA), with a target action date of August 21, 2025. The application is for adult and pediatric patients 12 years of age and older.
Key Findings from Clinical Studies
Data from the pivotal Phase 3 OASIS and OASISplus studies, along with three-year data from the Phase 2 open-label extension (OLE) study, were presented at the conference. These studies underscore donidalorsen's potential as a prophylactic treatment for HAE.
Kenneth Newman, M.D., senior vice president, head of clinical development at Ionis, stated, "Across the breadth of presentations at the congress, we believe the totality of the clinical evidence underscores the potential of donidalorsen to be the prophylactic treatment of choice for people living with HAE."
Impact on Quality of Life
New analyses from the OASISplus prospective switch cohort demonstrated donidalorsen's ability to reduce the HAE attack rate burden and improve quality of life in patients previously on other prophylactic treatments. The simplicity of monthly or every two-month self-administration via an autoinjector was also highlighted.
Long-Term Efficacy and Safety
Long-term analysis of the Phase 2 open-label extension study demonstrated a sustained mean reduction in HAE attack rates of 96% from baseline, maintained for up to three years. Across all three studies, donidalorsen was well-tolerated, 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.
Donidalorsen's Mechanism of Action
Donidalorsen is designed to target prekallikrein (PKK), which plays a crucial role in activating inflammatory mediators associated with acute HAE attacks. By reducing the production of PKK, donidalorsen aims to prevent HAE attacks prophylactically.
The Need for New HAE Treatments
HAE is a rare and potentially life-threatening genetic condition characterized by recurrent attacks of severe swelling. It is estimated to affect more than 20,000 people in the U.S. and Europe. While there have been advancements in HAE treatment, there remains a need for medicines that effectively reduce attacks, are well-tolerated, and are simple to administer.
Otsuka's Role
Otsuka Pharmaceutical Co., Ltd. has acquired exclusive rights to commercialize donidalorsen in Europe and the Asia-Pacific region, including Japan. The European Medicines Agency (EMA) has already accepted the Marketing Authorisation Application (MAA) for donidalorsen. Otsuka is preparing to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) this year.
