Donidalorsen Shows Durable Long-Term Efficacy for HAE, With Daniel Manning, MD

At the 2025 College of Allergy, Asthma, & Immunology (ACAAI) Annual Scientific Meeting in Orlando, Florida, Daniel E. Manning, MD, an allergy, asthma, & immunology specialist located in Arizona, presented long-term OASISplus open-label extension and switch data for donidalorsen (DAWNZERA) and what the findings mean for clinicians treating hereditary angioedema (HAE).1 For Dr. Manning, the message is clear: long-term data continue to reinforce donidalorsen’s strong safety and durable efficacy profile.

The US Food & Drug Administration (FDA) approved donidalorsen, an RNA-targeted medicine, as a prophylactic treatment for HAE earlier this year in adults and children aged ≥ 12 years. Ionis Pharmaceuticals announced the approval on August 21, 2025.2 The decision was based on pivotal data from the phase 3 OASIS-HAE and OASISplus trials, along with an ongoing phase 2 open-label extension trial.

In the extension study, donidalorsen performed well, with no new or unexpected safety signals. Patients experienced a 94–95% reduction in monthly attack rates, whether on every-4-week or every-8-week dosing. Manning noted that these reductions are comparable, or even superior, to what has been reported for previous long-term prophylactic options. Patients tended to experience continued improvement the longer they remained on therapy.

“The more you worry about it, the more attacks you're going to have,” Manning told HCPLive. “When you get a product like donidalorsen, and it is working well, you start going, ‘wow, I haven't had as few attacks. I've got an agent that's dosed less frequently than maybe other products I've used before.’ That builds this impetus of ‘I'm doing better, and life is great’ in that I'm not as stressed about dealing with my [HAE], which leads [to] a better quality of life and better control of the disease. The better you're doing, the better you do.”

Switch data from the study added another layer of insight. Patients who transitioned into donidalorsen from other prophylactic agents, including lanadelumab, C1 esterase inhibitors, and berotralstat, maintained disease control without rebound attacks. Most improved further, despite entering the study with relatively low baseline attack rates. More than 80% reported preferring donidalorsen over their prior therapy.

“When asked, ‘Well, do you like donidalorsen better than what you were on before? The vast majority said, ‘Yes, I feel better. I feel like my heart is [under] better control. I'm having fewer attacks. I'm tolerating it really well,” Manning said. “That was very telling in that even though patients were on some very good products, there's always room for improvement in patients who may not be [having an attack] as frequently as we think.”

Manning has no relevant reported disclosures.

References

1. Ionis presents new data demonstrating long-term disease control with DAWNZERATM (donidalorsen) at ACAAI 2025 Annual Meeting | Ionis Pharmaceuticals, Inc.. Ionis Pharmaceuticals, Inc. Published 2025. Accessed November 20, 2025. https://ir.ionis.com/news-releases/news-release-details/ionis-presents-new-data-demonstrating-long-term-disease-control

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