FDA Accepts Donidalorsen NDA for Hereditary Angioedema Prophylaxis
核心洞察
The FDA has accepted Ionis Pharmaceuticals (搜索)' NDA for donidalorsen, an investigational RNA-targeted medicine, for prophylactic treatment of hereditary angioedema (搜索) (HAE) in patients aged 12 and older.
Donidalorsen is designed to reduce prekallikrein (搜索) (PKK) production, interrupting the pathway that leads to HAE attacks, a rare genetic condition causing severe swelling.
The FDA has set a Prescription Drug User Fee Act (PDUFA) date of August 21, 2025, for donidalorsen, marking a significant step toward potential approval.
The FDA has accepted Ionis Pharmaceuticals (搜索)' New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted prophylactic medicine aimed at preventing attacks of hereditary angioedema (搜索) (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 (搜索) (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 (搜索) 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 (搜索) or HAE-C1INH-Type2 (搜索). 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.