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 hereditary angioedema (HAE).1,2

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,’” William Lumry, MD, 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.

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.