The FDA has approved Ionis Pharmaceuticals’ Dawnzera (donidalorsen) as the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in adults and pediatric patients ≥12 years. According to the company, approval was based on results from the Phase III OASIS-HAE trial, which showed that Dawnzera significantly reduced monthly HAE attacks versus placebo.¹

How does Dawnzera Change the Treatment Landscape for HAE Patients?

“Dawnzera represents a significant advance for people living with HAE who need improved treatment options,” said Brett P. Monia, PhD, CEO, Ionis, in a press release. “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. Importantly, the recently published switch data empowers patients and physicians with a roadmap for switching to Dawnzera from other prophylactic therapies…”

OASIS-HAE Trial Design and Endpoints

• The multi-center, double-blind, randomized, placebo-controlled OASIS-HAE trial evaluated the safety and efficacy of Dawnzera in 91 patients with HAE.
• Patients were randomly assigned in a 2:1 ratio to receive Dawnzera or placebo every four weeks (cohort A) or every eight weeks (cohort B).
• Within both cohorts, patients were randomly assigned in a 3:1 ratio to receive the treatment or a matching placebo.

• The primary endpoint of the trial was time-normalized investigator-confirmed (IC) HAE attack rate from week 1 to week 25.
• Key secondary endpoints included time-normalized IC HAE attack rate from week five to week 25, number of patients with a clinical response from week five to week 25, and the percentage of IC HAE attack patients who were attack-free from week five to week 25.²

Clinical Efficacy and Safety Results

• Results showed that Dawnzera reduced monthly HAE attacks by 81% compared to placebo over 24 weeks, with an 87% reduction from the second dose and ~90% reduction in moderate-to-severe attacks.
• Results from the ongoing OASISplus open-label extension showed sustained efficacy, with an up to 94% reduction in attack rate after one year and consistent results across both four- and eight-week dosing.
• Notably, a switch cohort in OASISplus indicated that patients previously on other prophylactic treatments experienced a 62% reduction in attacks after transitioning to Dawnzera.
• Dawnzera demonstrated a favorable safety profile. Common adverse events included injection site reactions, upper respiratory tract infections, urinary tract infections, and abdominal discomfort.¹

Expert Perspectives

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

Disease Context and Prevalence

• According to Rare Disease Advisor, HAE accounts for approximately 2% of clinical angioedema cases.
• Globally, HAE affects approximately one out of every 50,000 people, with prevalence rates estimated at between one out of every 10,000 people and one out of every 150,000 people.
• In the United States, HAE results in between 15,000 and 30,000 hospital visits annually.³

"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,” said OASIS-HAE and OASISplus trial investigator Marc Riedl, MD, MS, clinical director, US HAEA Angioedema Center; University of California, San Diego, in the press release. “Durable efficacy is essential in maintaining long-term disease control. Dawnzera is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment.”

References

1. DAWNZERA™ (donidalorsen) approved in the U.S. as first and only RNA-targeted prophylactic treatment for hereditary angioedema. BusinessWire. August 21, 2025. Accessed August 22, 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. OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE). Clinicaltrials.gov. Accessed August 22, 2025. https://clinicaltrials.gov/study/NCT05139810?term=OASIS-HAE&rank=1
3. Hereditary Angioedema (HAE). Rare Disease Advisor. Accessed August 22, 2025. https://www.rarediseaseadvisor.com/disease-info-pages/hereditary-angioedema-epidemiology/