William Lumry, MD: Founder of the Allergy & Asthma Specialists of Dallas

William Lumry, MD

Switching to Donidalorsen for HAE, With William Lumry, MD

Following its US Food & Drug Administration (FDA) approval on August 21, 2025, donidalorsen (Dawnzera) continues to draw attention not only for its novel RNA-targeted mechanism, but also for its robust real-world and long-term data showing its efficacy and safety across different patient groups, including those transitioning from other prophylactic treatments for 

During the open-label extension of the pivotal OASIS-HAE program, patients who had initially received placebo were switched to donidalorsen 80 mg every 4 weeks. These patients experienced a 62% further improvement in mean HAE attacks compared to baseline for previous prophylactic treatment. Over the course of a year, patients on the every-4 or -8-week regimen reached a ≥ 90% reduction, suggesting that both dosing intervals provide durable, long-term protection.

The switch study offered additional insight into real-world transitions. It evaluated patients who had previously been on other prophylactic medications, including oral berotralstat and subcutaneous therapies such as plasma kallikrein inhibitors or C1 esterase inhibitor replacement. When switched to donidalorsen, patients experienced an average 65% decrease in attack frequency compared to their prior treatment period.

“Now you can say, ‘Well, that may not be fair, because the reason that they switched may have been because they just weren't doing well on their previous prophylactic medication,’” 

 founder of the Allergy & Asthma Specialists of Dallas, told HCPLive. “But the point is…not everybody responds to every drug with different mechanisms of action, and those who don't do well on one type may do well on another type of prophylactic, and I think that that was very nicely demonstrated in the switch trial.”

Investigators carefully structured the transition protocol to maintain attack protection as the new therapy took effect. For example, oral berotralstat was continued for several weeks during the switch, while subcutaneous C1 esterase inhibitor replacement was tapered more gradually.

Despite these transitions, no new safety signals emerged. Across the placebo-controlled, open-label, and switch studies, donidalorsen demonstrated a favorable safety profile, with the most common adverse events being mild injection site reactions, upper respiratory infections, and urinary tract infections.

These findings underscore donidalorsen’s versatility, providing clinicians with a flexible, well-tolerated prophylactic option that maintains efficacy even in patients switching from other established HAE therapies. As long-term data continue to accumulate, donidalorsen is poised to play a significant role in improving disease control and quality of life for individuals living with HAE.

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 

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.

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Donidalorsen demonstrates strong efficacy in patients switching from other HAE prophylactic treatments. Lumry discusses pivotal data after FDA approval.

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 

attacks in adults and adolescents aged 12 years and older.

 The decision, announced August 21, 2025, marks the first approval of an RNA-targeted agent in this rare, potentially life-threatening condition.

, 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.”

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

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.


Lumry discuses donidalorsen, the first FDA-approved, RNA-targeted therapy for hereditary angioedema.

William Lumry, MD

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