FDA Approves Donidalorsen as First RNA-Targeted Prophylactic Treatment for Hereditary Angioedema

The FDA has approved donidalorsen (Dawnzera; Ionis Pharmaceuticals Inc), an 80 mg, self-administered subcutaneous autoinjector for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients aged 12 years and older. The approval makes donidalorsen the first and only RNA-targeted therapy approved for HAE, which is aimed at targeting plasma prekallikrein (PKK)—a protein that activates inflammatory mediators linked with acute attacks of HAE.¹

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“[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 DAWNZERA will be the prophylactic treatment of choice for many people living with HAE,” Brett P. Monia, PhD, chief executive officer of Ionis, said in a news release.¹

Hereditary Angioedema

HAE is estimated to impact around 7000 individuals that reside in the United States and is marked as a rare and potentially life-threatening genetic condition that causes recurrent attacks of severe swelling, or angioedema. The swelling commonly occurs in the hands, feet, genitals, stomach, face, and throat. In children, symptoms of HAE can occur as early as 2 years of age, and nearly half of children with HAE present symptoms by age 10. Signs and symptoms include visible swelling; nausea, vomiting, diarrhea, and abdominal pain related to swelling in the gastrointestinal tract; difficulty swallowing; and a gasping sound caused by mouth and throat swelling.²

"People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful, and dangerous breakthrough attacks even with current treatments. Durable efficacy is essential in maintaining long-term disease control.” Marc Riedl, MD, MS, clinical director of the US HAEA Angioedema Center, University of California, San Diego, and OASIS-HAE and OASISplus trial investigator, said in the news release. “[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.”¹

OASIS-HAE and OASISplus Study Data

The approval for donidalorsen is based on positive findings from the phase 3, global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE study (NCT05139810), which successfully met its primary end point. In the study, donidalorsen, administered once every 4 weeks (Q4W), significantly reduced the monthly HAE attack rate by 81% compared with placebo over a 24-week period. When measured from the second dose, the mean attack rate reduction increased to 87%, meeting the study’s secondary end point. Additionally, the study authors noted that donidalorsen Q4W reduced moderate-to-severe HAE attacks by nearly 90% over the same 24-week period, also when measured from the second dose.^1,3

The results are confirmed by the ongoing OASISplus open-label extension study (NCT05392114), which found that 80 mg of donidalorsen self-administered once every 8 weeks (Q8W) demonstrated similar effects as Q4W. Additionally, donidalorsen had a 94% total mean attack rate reduction from baseline in both dosing groups after 1 year of treatment.^1,4

After conducting a switch cohort analysis with donidalorsen and patients treated with lanadelumab (Takhzyro; Takeda), C1-esterase inhibitor, or berotralstat (Orladeyo; BioCryst) for at least 12 weeks, donidalorsen reduced the mean HAE attack rate by 62% from prior prophylactic treatment. Additionally, a total of 84% of surveyed patients preferred donidalorsen over their previous prophylactic treatment due to its better disease control, shorter admission time, and less injection site pain or reactions.¹

In both OASIS-HAE and OASISplus, the most common adverse events included site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort.¹

“As the first FDA-approved RNA-targeted therapy for HAE, [donidalorsen] represents a welcome advance in therapeutic options for preventing attacks. Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” Anthony J. Castaldo, CEO & chairman of the board at US Hereditary Angioedema Association (HAEA) and Hereditary Angioedema International (HAEi), said in the news release.¹

REFERENCES

1. DAWNZERA™ (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema. Ionis. News release. August 21, 2025. Accessed August 21, 2025. https://ir.ionis.com/news-releases/news-release-details/dawnzeratm-donidalorsen-approved-us-first-and-only-rna-targeted

2. Cleveland Clinic. Hereditary Angioedema. News release. Updated March 31, 2025. Accessed August 21, 2025. https://my.clevelandclinic.org/health/diseases/hereditary-angioedema

3. OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE). Updated March 3, 2025. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT05139810

4. A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE) Updated June 24, 2025. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT05392114