FDA Approves Breakthrough RNA Therapy for Hereditary Angioedema
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Washington, D.C. – August 22,2025 – In a landmark decision for patients battling a rare and potentially life-threatening genetic condition,the U.S. Food and Drug Administration (FDA) today approved donidalorsen,marketed as DAWNZERA by ionis Pharmaceuticals,for the prevention of hereditary angioedema (HAE) attacks.This approval marks the first time a therapy targeting RNA has been authorized to treat HAE, offering a novel approach to managing the debilitating symptoms of this disease.
Understanding Hereditary angioedema
Hereditary angioedema is a rare, inherited disorder characterized by recurrent episodes of swelling in various parts of the body, including the limbs, face, gastrointestinal tract, and airway. Approximately 7,000 individuals in the United States are affected by HAE 1.These attacks can be painful and, in severe cases involving the airway, life-threatening. The condition stems from a deficiency or dysfunction of the C1 esterase inhibitor protein, leading to excessive bradykinin production and subsequent inflammation.
Did You Know? HAE attacks are frequently enough unpredictable and can occur without any obvious triggers, making management particularly challenging for patients.
DAWNZERA: A New Prophylactic Approach
Donidalorsen works by inhibiting plasma prekallikrein, a key protein involved in the activation of inflammatory pathways that drive HAE attacks. Administered via a subcutaneous autoinjector, DAWNZERA offers flexible dosing schedules of either once every four weeks (Q4W) or every eight weeks (Q8W). This convenience aims to improve adherence and quality of life for individuals managing this chronic condition.
OASIS-HAE Trial Results
The FDA’s decision was based on compelling data from the Phase 3 OASIS-HAE trial (NCT05139810), a randomized, double-blind, placebo-controlled study involving 90 participants.The trial demonstrated a significant reduction in attack rates with donidalorsen compared to placebo.
| Treatment Group | Mean Attack Rate Reduction vs. Placebo | P-value |
|---|---|---|
| Donidalorsen Q4W | 81% | <.001 |
| Donidalorsen Q8W | 55% | .004 |
| Placebo | – | – |
Specifically,the Q4W regimen reduced the mean attack rate by 81% compared to placebo (95% CI,65-89; P<.001), while the Q8W regimen showed a 55% reduction (95% CI, 22-74; P=.004) 2. Patients receiving the Q4W dose also reported improvements in health-related quality of life,as measured by the Angioedema Quality-of-Life Questionnaire.
Pro Tip: Prophylactic treatments like DAWNZERA are designed to prevent attacks, while on-demand therapies are used to treat attacks as they occur. Discuss the best approach with your healthcare provider.
durability and Patient Preference
Data from the ongoing OASISplus open-label extension study further support the long-term efficacy of donidalorsen. Both dosing regimens maintained a 94% reduction in mean attack rate after one year. Notably, patients who switched from other prophylactic treatments – including lanadelumab, C1-esterase inhibitor, and berotralstat – experienced a 62% reduction in attack rates with donidalorsen, and 84% reported a preference for the new therapy.
Safety and Tolerability
Clinical trials indicated that donidalorsen is generally well-tolerated. The most commonly reported adverse reactions included injection site reactions, upper respiratory tract infections, urinary tract infections, and abdominal discomfort. The majority of adverse events were mild or moderate in severity.
Expert Reactions
“DAWNZERA represents a welcome advance in therapeutic options for preventing attacks,” stated Anthony J. Castaldo, CEO and board chairman of the US Hereditary Angioedema Association and Hereditary Angioedema International. “Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs.”
Marc riedl, MD, MS, clinical director at the US HAEA Angioedema Center, University of California, San Diego, and a trial investigator, emphasized the importance of durable efficacy. “People living with HAE manage this condition for all their lives…DAWNZERA is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks.”
What are your thoughts on the potential impact of RNA-targeted therapies on rare disease treatment? How might this approval influence the future of HAE management?
References:
- DAWNZERA™ (donidalorsen) approved in the U.S.as first and only RNA-targeted prophylactic treatment for hereditary angioedema.Ionis Pharmaceuticals. August 21, 2025. Accessed August 22, 2025.
- Riedl MA, Tachdjian R, Lumry WR, et al. Efficacy and Safety of Donidalorsen for Hereditary Angioedema. N Engl J Med. 2024;391(1):21-31. doi:10.1056/NEJMoa2402478
Hereditary angioedema has historically been a challenging condition to treat, with limited prophylactic options. The growth of donidalorsen signifies a paradigm shift in HAE management, leveraging the power of RNA-targeted therapies. This approach holds promise for other genetic disorders as well, potentially opening new avenues for treatment development. ongoing research is focused on optimizing dosing regimens and identifying biomarkers to predict treatment response.
What is hereditary angioedema (HAE)?
HAE is a rare genetic disorder causing recurrent episodes of swelling in various body parts, potentially life-threatening if the airway is affected.
How does donidalorsen (DAWNZERA) work?
DAWNZERA inhibits plasma prekallikrein, a protein involved in triggering HAE attacks, offering a novel RNA-targeted approach.
What are the common side effects of donidalorsen?
Common side effects include injection site reactions, upper respiratory infections, and urinary tract infections, generally mild to moderate in severity.
How often is donidalorsen administered?
DAWNZERA is administered via subcutaneous injection, with dosing options of once every four weeks or every eight weeks.
Is donidalorsen approved for children?
Yes,DAWNZERA is approved for use in adult and pediatric patients aged 12 years and older.
Disclaimer: This article provides general details and should not be considered medical advice. Please consult with a qualified healthcare professional for diagnosis and treatment of any medical condition.
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