FDA Accepts New Drug Application for Donidalorsen for Hereditary Angioedema
Key Insights
The FDA has accepted a new drug application for donidalorsen, an RNA-targeting drug, for prophylactic treatment of hereditary angioedema (search) (HAE) in patients 12 years and older.
Clinical data from Phase 3 OASIS-HAE, OASISplus studies, and an ongoing Phase 2 open-label extension study support the application, demonstrating a 96% reduction in HAE attacks.
Donidalorsen offers convenient monthly or bi-monthly self-administration via autoinjector and has shown a favorable safety profile with mainly injection-site reactions as adverse events.
The U.S. Food and Drug Administration (FDA) has accepted a new drug application (NDA) for donidalorsen, a prophylactic RNA-targeting therapy developed by Ionis Pharmaceuticals, for the prevention of hereditary angioedema (search) (HAE) attacks in patients aged 12 years and older. This decision marks a significant step forward in addressing the unmet needs of individuals living with this rare and potentially life-threatening genetic condition.
Clinical Evidence Supporting Donidalorsen
The NDA submission was based on compelling results from the Phase 3 OASIS-HAE and OASISplus studies, as well as data from an ongoing Phase 2 open-label extension (OLE) study. These studies demonstrated that donidalorsen achieved a sustained mean reduction rate of 96% in HAE attacks from baseline, a result that was maintained for up to three years in the ongoing Phase 2 OLE study. The data were presented at the American College of Asthma, Allergy & Immunology Annual Scientific Meeting in October.
Kyle Jenne, executive vice president and chief global product strategy officer at Ionis, emphasized the impact of HAE on patients' lives, stating, "Hereditary angioedema (search) (HAE) is a rare genetic disease where patients experience recurring and unpredictable attacks of severe swelling, which can be life-threatening. The unpredictability of attacks can greatly impact daily life. Despite currently available prophylactic treatments, many patients continue to experience painful and potentially life-threatening breakthrough attacks."
Safety and Tolerability
In addition to its efficacy, donidalorsen has demonstrated a favorable safety and tolerability profile in clinical trials. The most common treatment-emergent adverse events were injection-site reactions, with no serious treatment-emergent adverse events reported.
Convenience of Administration
Donidalorsen offers the convenience of monthly or every-other-month self-administration via an autoinjector, an attribute that healthcare professionals are looking for in a prophylactic treatment. This ease of use has the potential to improve patient adherence and quality of life.
Addressing Unmet Needs in HAE Treatment
Despite available prophylactic treatments, many HAE patients continue to experience breakthrough attacks, highlighting the urgent need for more effective and convenient therapies. Donidalorsen's unique profile, combining high efficacy, a favorable safety profile, and convenient administration, may address these unmet needs.
Regulatory Timeline
The FDA has set an action date of August 21, 2025, for its decision on the approval of donidalorsen. If approved, donidalorsen has the potential to be Ionis’ second independent commercial launch.