
FDA Approves First RNA-Targeted Treatment for Hereditary Angioedema
Key Takeaways
- Donidalorsen is the first RNA-targeted prophylactic treatment approved for hereditary angioedema, offering significant attack rate reduction.
- The OASIS-HAE study showed an 81% reduction in HAE attacks with 4-week dosing, increasing to 87% from the second dose.
The approval makes donidalorsen the only treatment in the US for hereditary angioedema that is an RNA-targeted prophylactic.
The treatment of
“[Donidalorsen] represents a significant advance for people living with HAE who need improved treatment options. With strong and durable efficacy, convenient administration, and the longest dosing option available, we believe [donidalorsen] will be the prophylactic treatment of choice for many people living with HAE,” said Brett P. Monia, PhD, CEO of Ionis, in a statement.1
The approval comes based on the results of the phase 3 study,
Donidalorsen is self-administered in 80-mg doses through a subcutaneous autoinjector. The dose can be taken every 4 weeks or every 8 weeks.
The OASIS-HAE study included 90 patients overall, of which 45 patients took the dose every 4 weeks and 23 patients took the dose every 8 weeks. Although the dose taken every 4 weeks was more effective than every 8 weeks, the OASIS-HAE study proved that a dose taken every 8 weeks was still more effective than placebo.2
The mean attack rate for participants taking the dose every 8 weeks was 55% lower (95% CI, 22%-74%) compared with placebo and the median reduction in attack rate was 83% compared with only 16% in the placebo group. Further, the mean attack rate from weeks 5 to 25 was 60% lower in the 8-week dose group compared with placebo. These results, along with the results of those who received the dose every 4 weeks, proves that donidalorsen was effective in reducing the number of attacks.
The treatment was well tolerated, with the most common adverse reactions being injection site reactions, urinary tract infections, upper respiratory tract infections, and abdominal discomfort. All of these were reported by 5% or more of the study group.
"[Donidalorsen] is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time, and reduced burden of treatment,” said Marc Riedl, MD, MS, clinical director of US HAEA Angioedema Center at the University of California, San Diego.1
References
1. Dawnzera (donidalorsen) approved in the US as first and only RNA-targeted prophylactic treatment for hereditary angioedema. News release. Business Wire. August 21, 2025. Accessed August 21, 2025.
2. Riedl MA, Tachdijian R, Lumry WR, et al. Efficacy and safety of donidalorsen for hereditary angioedema. N Engl J Med. 2024;391:21-31. doi:10.1056/NEJMoa2402478
3. Hereditary angioedema. Cleveland Clinic. Updated March 31, 2025. Accessed August 21, 2025.
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