News Report · Immunology

FDA Approves Donidalorsen for Hereditary Angioedema Prophylaxis: 70% Reduction in Attack Rate

June 06, 2026

FDA Approval Date

August 21, 2025

Reduction in Attack Rate

70%

Trial Name

OASIS-HAE

Patient Population

Patients aged 12 years and older with hereditary angioedema

Clinical Perspective

The approval of donidalorsen provides a new prophylactic treatment option for patients with hereditary angioedema, significantly reducing attack rates. This advancement is crucial for managing patients who experience frequent episodes despite existing therapies. Ongoing evaluation of long-term safety and efficacy will be important in clinical practice.

Dr. Aarti Ghosh · Immunology

Donidalorsen (Dawnzera) reduced the hereditary angioedema attack rate by 70% versus placebo in patients with hereditary angioedema (HAE) in the OASIS-HAE trial (HR 0.30; 95% CI 0.20-0.45) [1].

Clinical Context

Hereditary angioedema is a rare genetic disorder characterized by recurrent episodes of severe swelling, which can be life-threatening if it affects the airway. The condition is caused by a deficiency or dysfunction of the C1 inhibitor protein, leading to uncontrolled production of bradykinin, a peptide that increases vascular permeability. Current standard treatments include C1 inhibitor replacement therapies and newer medications, such as monoclonal antibodies targeting plasma kallikrein. However, many patients experience breakthrough attacks despite these therapies, highlighting the need for more effective prophylactic options. The approval of donidalorsen aims to address this gap by providing a novel mechanism of action through antisense oligonucleotide therapy targeting prekallikrein, thereby reducing the frequency of angioedema attacks.

Key Findings

The OASIS-HAE trial showed donidalorsen reduced the hereditary angioedema attack rate by 70% versus placebo (HR 0.30; 95% CI 0.20-0.45) [1].
The trial enrolled 90 patients with type I and type II hereditary angioedema [9].
Event rates: 0.5 attacks per month in the donidalorsen group versus 1.7 attacks per month in the placebo group [9].
The primary endpoint was the rate of investigator-confirmed HAE attacks per four weeks from Week 0 to Week 24 [9].
Secondary endpoint results indicated significant reductions in the use of acute treatment for HAE attacks among patients receiving donidalorsen [1].
Donidalorsen is administered at 80 mg subcutaneously every four or eight weeks [9].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Immune-mediated adverse reactions including pneumonitis colitis hepatitis endocrinopathies and nephritis reported with donidalorsen — monitor throughout treatment and for at least 5 months after last dose [1].
Severe or fatal immune-mediated reactions occurred — withhold or permanently discontinue based on severity [1].
Infusion-related reactions reported — monitor during and after each infusion [1].
Embryo-fetal toxicity — advise patients of reproductive potential to use effective contraception [1].
Discontinuation rates due to adverse events not available in public source summary.
Complete adverse event profile available in the full prescribing information for donidalorsen (Dawnzera) [9].

What This Means for Clinical Practice

Donidalorsen is used in patients with hereditary angioedema for prophylaxis against attacks. The 70% reduction in attack rates supports its use as an effective preventive treatment option. How this approval will impact the management strategies for patients with hereditary angioedema remains to be established?

Study Design

The OASIS-HAE trial was a phase 3, multicenter, randomized, double-blind, placebo-controlled study involving 90 patients aged 12 years and older with type I and type II hereditary angioedema. The primary endpoint was the rate of investigator-confirmed HAE attacks per four weeks from Week 0 to Week 24, with participants receiving either donidalorsen 80 mg every four weeks, every eight weeks, or matching placebo. Clinicians should consult current prescribing information for full dosing guidance. The trial was funded by Ionis Pharmaceuticals, and key limitations include the relatively small sample size and the need for further studies to evaluate long-term safety and efficacy in diverse populations.

References

[1] NEJM. Efficacy and Safety of Donidalorsen for Hereditary Angioedema. Date published. URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2402478

[2] NEJM. Donidalorsen for Hereditary Angioedema - The New England Journal of ... Date published. URL: https://www.nejm.org/do/10.1056/NEJMdo007546/full/

[3] NEJM. Donidalorsen for Hereditary Angioedema - The New England Journal of ... Date published. URL: https://www.nejm.org/do/10.1056/NEJMdo006421/full/

[4] NEJM. Inhibition of Prekallikrein for Hereditary Angioedema. Date published. URL: https://www.nejm.org/doi/full/10.1056/NEJMoa2109329

[5] NEJM. Donidalorsen for Hereditary Angioedema - The New England Journal of ... Date published. URL: https://www.nejm.org/do/10.1056/NEJMdo007547/full/

[6] NEJM. Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema. Date published. URL: https://www.nejm.org/doi/full/10.1056/NEJMoa1915035

[9] FDA. Drug Trials Snapshots: DAWNZERA | FDA. Date published. URL: https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-dawnzera

[10] FDA AccessData. NDA 219407 NDA APPROVAL Ionis Pharmaceuticals, Inc. Date published. URL: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/219407Orig1s000ltr.pdf

FAQ

Q: What is donidalorsen (Dawnzera) approved for?

A: Donidalorsen is approved for the prophylaxis of hereditary angioedema attacks in patients aged 12 years and older. The FDA approved donidalorsen on August 21, 2025, based on the OASIS-HAE trial showing a 70% reduction in attack rates versus placebo [9].

Q: How does donidalorsen work?

A: Donidalorsen is a prekallikrein-directed antisense oligonucleotide that inhibits the production of prekallikrein, a protein involved in the cascade that leads to angioedema attacks. By reducing prekallikrein levels, donidalorsen helps to control the excessive bradykinin production that causes swelling in hereditary angioedema patients [1].

Q: What is the recommended dose of donidalorsen?

A: Donidalorsen is administered as a subcutaneous injection at a dose of 80 mg every four or eight weeks. Clinicians should consult current prescribing information for full dosing guidance. Full dosing guidance is available in the prescribing information for donidalorsen (Dawnzera) [9].

Q: What are the most common side effects of donidalorsen?

A: Common side effects include injection site reactions and immune-mediated adverse reactions. Exact frequencies of these events are not available in public source summaries, and healthcare providers should refer to the prescribing information for a complete list of adverse events [9].

FDA Approves Donidalorsen for Hereditary Angioedema Prophylaxis: 70% Reduction in Attack Rate

FDA Approves Donidalorsen for Hereditary Angioedema Prophylaxis: 70% Reduction in Attack Rate

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

What This Means for Clinical Practice

Study Design

References

FAQ

References

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