FDA’s Approval of Donidalorsen for HAE, With William Lumry, MD

The US Food and Drug Administration (FDA) has approved donidalorsen (Dawnzera), an RNA-targeted therapy, for the prevention of hereditary angioedema (HAE) attacks in adults and adolescents aged 12 years and older.1,2 The decision, announced August 21, 2025, marks the first approval of an RNA-targeted agent in this rare, potentially life-threatening condition.

In an interview with HCPLive, William Lumry, MD, founder of the Allergy & Asthma Specialists of Dallas, explained how donidalorsen’s mechanism differs from existing prophylactic options. Donidalorsen is an antisense oligonucleotide designed to reduce the production of prekallikrein, preventing the formation of plasma kallikrein, a key driver of bradykinin-mediated vascular leakage and swelling.

“This is the first time that prekallikrein has been targeted as a potential regulating protein in this cascade,” Lumry said. “Just about everywhere on this cascade has been targeted by prophylactic medications and some acute therapy for the swelling attacks when they occur, but this is the first one that actually is…preventing the cascade from going forward.”

The FDA approval followed compelling efficacy and durability data from the phase 3 OASIS-HAE and OASISplus trials, alongside the ongoing phase 2 open-label extension (OLE). In OASIS-HAE, donidalorsen achieved an 81% reduction in monthly HAE attacks with every-4-week dosing and a 55% reduction with every-8-week dosing compared to placebo. More than half of patients on the 4-week regimen remained completely attack-free between weeks 4 and 24.

The OASISplus and the OLE trial exhibited donidalorsen’s durability of response. Patients who switched from other prophylactic therapies, including lanadelumab and C1 esterase inhibitors, saw additional reductions in attack frequency, with some achieving over 90% improvement from baseline. Long-term data have shown sustained efficacy through 3 years, with a mean reduction of 96% in HAE attacks. Quality-of-life scores also improved, and most patients preferred donidalorsen to their prior prophylaxis.

Across trials, donidalorsen demonstrated a favorable safety profile, with no serious treatment-related adverse events observed. Injection site reactions were the most common adverse events, typically mild or moderate.

For clinicians, donidalorsen adds a distinct mechanism and extended dosing flexibility—potentially every 8 weeks—to the HAE treatment armamentarium. As Dr. Lumry emphasized, “This new mechanism may provide benefit to those who don't respond to other prophylactic medications, plus it's also a way to decrease or to control this system with relatively infrequent dosing of a medication, so the patients may be able to dose once every 4 weeks or and once their disease is controlled, then once every 8 weeks, which is the first prophylactic medication with a potential 8-week dosing interval.”

References

1. Derman C. FDA Approves Donidalorsen to Prevent Hereditary Angioedema Attacks. Hcplive.com. Published August 21, 2025. Accessed October 7, 2025. https://www.hcplive.com/view/fda-approves-donidalorsen-to-prevent-hereditary-angioedema-attacks

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