FDA Approves First RNA-Targeted Treatment for Hereditary Angioedema

The treatment of hereditary angioedema (HAE) takes a new step forward with the FDA approval of donidalorsen (Dawnzera; Ionis Pharmaceuticals, Inc),¹ an RNA-targeted prophylactic treatment. The approval makes donidalorsen the only treatment of its kind to help prevent attacks of HAE in patients 12 years and older.

Donidalorsen can be used to treat hereditary angioedma, which causes swelling in the body. | Image credit: B-design - stock.adobe.com

“[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, OASIS-HAE (NCT05139810), which was a global, multicenter, randomized trial conducted among patients living with HAE.² Donidalorsen taken every 4 weeks was found to decrease the monthly attack rate for HAE by 81% (95% CI, 65%-89%) through 24 weeks. This mean reduction in attack rate increased to 87% (95% CI, 72%-94%) when researchers measured starting at the second dose. The median reduction in attack rate from baseline was 90% in those who received the medication every 4 weeks.

HAE is a genetic disorder that attacks different parts of the body via build up of fluid from tiny blood vessels that can prevent blood and lymph from moving throughout the body. This can result in swelling of different areas of the body, including the face and hands.³ This swelling can also extend to internal organs that are not seen, such as digestive organs or airways. The severity of the condition can vary, with the swelling of internal organs possibly life-threatening without proper treatment. The condition is rare, affecting approximately 7000 people in the US.

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. https://www.businesswire.com/news/home/20250818615141/en/DAWNZERA-donidalorsen-approved-in-the-U.S.-as-first-and-only-RNA-targeted-prophylactic-treatment-for-hereditary-angioedema

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. https://my.clevelandclinic.org/health/diseases/hereditary-angioedema