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FDA Approves Donidalorsen to Prevent Hereditary Angioedema Attacks
The FDA has approved Ionis Pharmaceuticals' donidalorsen to prevent HAE attacks in adults and children over 12 years.
The US Food and Drug Administration (FDA) has approved donidalorsen (DAWNZERA), an RNA-targeted medicine, to prevent hereditary angioedema (HAE) attacks in adults and children aged 12 years or older. Ionis Pharmaceuticals announced the approval on August 21, 2025.1
"[Donidalorsen] is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment," said OASIS-HAE and OASISplus trial investigator Marc Riedl, MD, MS, clinical director at US HAEA Angioedema Center; University of California, San Diego.1
The decision follows an Orphan Drug Designation in 2023 and is supported by pivotal data from the phase 3 OASIS-HAE and OASISplus trials, along with findings from the ongoing phase 2 OLE trial.2 Studies assessed monthly and bi-monthly dosing of donidalorsen, which targets prekallikrein, a protein that drives the pathway leading to HAE attacks.
Across all 3 trials, donidalorsen provided significant and sustained reductions in HAE attacks. In the ongoing phase 2 OLE trial, donidalorsen achieved a sustained mean reduction of 96% in HAE attack rate from baseline through 3 years.2
In OASIS-HAE, patients were treated with donidalorsen 80 mg via subcutaneous injection every 4 or 8 weeks.3 The study met its primary endpoint, demonstrating an 81% lower monthly HAE attack rate with donidalorsen every 4 weeks compared to placebo (P < .001) and a 55% reduction with donidalorsen every 8 weeks. At week 25, 91% of patients on donidalorsen every 4 weeks were well-controlled, measured by the Angioedema Control test.
In OASISplus, the open-label extension cohort assessed patients switching from both newer oral and injectable long-term prophylactic treatments to donidalorsen. In this extension, attack rates continued to improve over time, resulting in 93% and 92% improvement from baseline among patients taking donidalorsen every 4 or 8 weeks, respectively.3 Patients had an improved quality of life, with AE-QoL scores improved by 28 points and 24 points from baseline to week 25 among patients taking donidalorsen every 4 or 6 weeks, respectively.
Patients who switched to donidalorsen from prior prophylactic treatment, such as lanadelumab, berotralstat, or C1-esterase inhibitor, experienced 62% further improvement in mean monthly HAE attack rate compared to baseline.3 Moreover, 84% of patients who switched preferred donidalorsen over previous prophylactic treatment.
The 3 trials also showed that donidalorsen was well-tolerated, with no serious treatment-emergent adverse events. Most adverse events were mild or moderate, and injection site reactions were the most common.2
HAE, a rare, potentially life-threatening genetic disorder, affects more than 20,000 patients in the US and Europe.2 For patients who still experience painful attacks with currently available treatments, donidalorsen can offer another option.
"As the first FDA-approved RNA-targeted therapy for HAE, DAWNZERA represents a welcome advance in therapeutic options for preventing attacks. Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” said Anthony J. Castaldo, CEO & chairman of the board, U.S. Hereditary Angioedema Association and Hereditary Angioedema International, in a statement.1
References
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.
Ionis Pharmaceuticals. Ionis announces FDA acceptance of New Drug Application for donidalorsen for prophylactic treatment of HAE. November 4, 2024. Accessed August 18, 2025. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-fda-acceptance-new-drug-application-donidalorsen.
Ionis Pharmaceuticals. Ionis presents positive results from OASIS-HAE and OASISplus studies of investigational medicine donidalorsen in patients with hereditary angioedema. May 31, 2024. Accessed August 18, 2025. https://ir.ionis.com/news-releases/news-release-details/ionis-presents-positive-results-oasis-hae-and-oasisplus-studies.
