The FDA has accepted Ionis Pharmaceuticals' New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted prophylactic medicine aimed at preventing attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. This decision marks a significant step forward in addressing the needs of individuals affected by this rare and potentially life-threatening genetic condition.
HAE is characterized by recurrent episodes of severe swelling in various body parts, including the feet, hands, genitals, stomach, face, and throat. The condition arises from a deficiency or dysfunction of the C1-INH protein. Donidalorsen is designed to reduce the production of prekallikrein (PKK), thereby interrupting the pathway that leads to HAE attacks.
The FDA has set a Prescription Drug User Fee Act (PDUFA) date of August 21, 2025, for donidalorsen. "Based on the totality of clinical evidence from the Phase 3 OASIS-HAE and OASISplus studies, as well as new 3-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, PhD, chief executive officer of Ionis, in a press release.
Clinical Trial Data
Ionis Pharmaceuticals presented positive data from the Phase 3 OASIS-HAE study (NCT05139810) of donidalorsen at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Meeting. The multicenter, double-blind, placebo-controlled, and randomized trial included patients aged 12 years and older with HAE-C1INH-Type1 or HAE-C1INH-Type2. Patients received either 80 mg of donidalorsen or a placebo subcutaneously once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over a 24-week period.
Patient-Reported Outcomes
Results from the OASIS-HAE study demonstrated that patients receiving donidalorsen Q4W or Q8W reported statistically significant improvements in quality of life (QoL), relative to pooled placebo, in terms of functioning, fears/shame, and nutrition. A significantly larger proportion of the donidalorsen Q4W group achieved the minimal clinically important difference (MCID) in Angioedema Quality of Life Questionnaire (AE-QoL) total score from baseline to week 24 compared to the placebo group.
Most patients in both donidalorsen groups reached the MCID in AECT total score at Week 24 (90.2% Q4W group; 68.2% Q8W group). Additionally, approximately half of patients in each donidalorsen group reported complete disease control (AECT = 16) at Week 24 (51.1% Q4W group; 47.8% Q8W group).
Safety and Tolerability
Across all studies presented at ACAAI, donidalorsen was well-tolerated, with no serious treatment-emergent adverse events related to the treatment.
