Drug Update · Immunology

FDA Approves Donidalorsen for HAE: 81% Lower Attack Rate

July 18, 2026

Approval date

2025-08-21

Indication

Prophylaxis to prevent attacks of hereditary angioedema in adult and pediatric patients 12 years and older

Primary efficacy

81% lower HAE attack rate with donidalorsen 80 mg q4wks vs placebo (LS mean 0.44 vs 2.26 attacks/4 weeks)

Trial

OASIS-HAE, phase 3 randomized double‑blind placebo‑controlled (N=90)

Recommended dose

80 mg subcutaneously every 4 weeks; 80 mg every 8 weeks may be considered

Clinical Perspective

Allergists, immunologists, and clinicians managing hereditary angioedema can now prescribe DAWNZERA (donidalorsen) for prophylaxis to prevent HAE attacks in adults and pediatric patients 12 years and older ^[2]^[3]. The OASIS-HAE results support using donidalorsen 80 mg subcutaneously every 4 weeks (with an every‑8‑weeks option) to markedly reduce attack rates and increase attack‑free proportions compared with placebo ^[1]^[2]^[3]. What are the longer‑term safety and effectiveness outcomes of donidalorsen beyond the 24‑week trial period reported in OASIS-HAE?

Dr. Aarti Ghosh · Immunology

The FDA approved DAWNZERA (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older on 2025-08-21 based on the OASIS-HAE trial, which showed an 81% lower investigator‑confirmed HAE attack rate with donidalorsen 80 mg every 4 weeks versus placebo ^[2]^[3]^[1]. Clinicians should consult current prescribing information for full dosing guidance. The approval and prescribing information recommend 80 mg subcutaneously every 4 weeks, with an 80 mg every‑8‑weeks option ^[2]^[3].

Clinical Context

Donidalorsen is a prekallikrein‑directed antisense oligonucleotide (ASO‑GalNAc conjugate) that reduces prekallikrein (PKK) expression and thereby lowers plasma kallikrein activity and bradykinin generation implicated in HAE attacks ^[2]^[3]. The agent is developed and marketed by Ionis Pharmaceuticals (DAWNZERA) and was evaluated in the phase 3 OASIS-HAE program ^[1]^[3]. The NEJM report framed HAE as a disorder of kallikrein‑kinin dysregulation and noted long‑term prophylaxis can stabilize this system; donidalorsen specifically reduces prekallikrein expression to achieve prophylactic effect ^[1]^[2].

Key Findings

The OASIS-HAE trial showed donidalorsen 80 mg subcutaneously every 4 weeks reduced the least‑squares mean investigator‑confirmed HAE attack rate to 0.44 attacks per 4 weeks versus 2.26 attacks per 4 weeks with placebo (an 81% lower attack rate; P<0.001) ^[1]^[3].
Clinicians should consult current prescribing information for full dosing guidance.
Donidalorsen 80 mg every 8 weeks reduced the attack rate to a least‑squares mean of 1.02 attacks per 4 weeks versus 2.26 with placebo, a 55% lower attack rate (P = 0.004) ^[1]^[3].
Median reductions in attack rate from baseline were 90% in the 4‑week group, 83% in the 8‑week group, and 16% in the placebo group; the proportion of patients who were attack‑free from Week 4 to Week 24 was 53% (80 mg q4wks), 35% (80 mg q8wks), and 9% (placebo) ^[1]^[3].
Predefined secondary endpoints (weeks 4–24) showed reductions in moderate or severe attack rate, attacks requiring acute therapy, and higher proportions achieving ≥50%, ≥70%, and ≥90% reductions from baseline in the donidalorsen arms versus placebo ^[3].

Safety & Tolerability

Erythema at the injection site (injection site reactions) ^[1]^[2].
Headache ^[1]^[2].
Nasopharyngitis / upper respiratory tract infection ^[1]^[2].
Urinary tract infection ^[2].
Abdominal discomfort ^[2].
Hypersensitivity reactions, including anaphylaxis, have been reported ^[2].
Reduction in platelet count: mean percent change in platelet count at Week 25 was -9.6% (80 mg q4wks), -7.9% (80 mg q8wks), and -1.4% (placebo); no patient treated with donidalorsen had a platelet count <50,000/mm3 in the reported studies ^[2].
Clinicians should consult current prescribing information for full dosing guidance.
Increases from baseline in liver enzymes (ALT, AST, GGT) were observed; increased levels were generally below 3 times the upper limit of normal and stabilized, and discontinuations for LFT increases were infrequent ^[2].

Study Design

OASIS-HAE was a phase 3, multicenter, randomized, double‑blind, placebo‑controlled trial that enrolled 90 adult and pediatric patients 12 years and older with Type I or Type II HAE who had at least 2 investigator‑confirmed attacks during an 8‑week run‑in; patients were randomized to donidalorsen 80 mg subcutaneously every 4 weeks (n=45), 80 mg every 8 weeks (n=23), or placebo (n=22) ^[1]^[3]. Clinicians should consult current prescribing information for full dosing guidance. The primary endpoint was the time‑normalized number of investigator‑confirmed HAE attacks per 4 weeks (attack rate) from week 1 to week 25 (reported as Week 0 to Week 24 in prescribing documentation) ^[1]^[3].

FAQ

Q1 What is DAWNZERA (donidalorsen) approved for?

DAWNZERA (donidalorsen) is approved for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. The FDA approval was based on the OASIS-HAE phase 3 trial demonstrating reductions in investigator‑confirmed HAE attack rates compared with placebo.

Q2 How does donidalorsen work?

Donidalorsen is a prekallikrein‑directed antisense oligonucleotide (ASO‑GalNAc conjugate) that binds PKK mRNA and causes RNase H1‑mediated degradation, reducing PKK production. Lower PKK reduces plasma kallikrein activity and bradykinin generation, mechanisms implicated in HAE attacks, thereby preventing excessive bradykinin production in patients with HAE.

Q3 What is the recommended dose of donidalorsen?

The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg administered subcutaneously every 8 weeks may also be considered. DAWNZERA is supplied as an 80 mg/0.8 mL single‑dose autoinjector and is intended for subcutaneous administration; patients should be trained on proper autoinjector use and storage instructions in the full prescribing information.

Q4 What are the most common side effects of donidalorsen?

The most common adverse reactions reported include injection site reactions (erythema and related local reactions), headache, upper respiratory tract infection or nasopharyngitis, urinary tract infection, and abdominal discomfort. Hypersensitivity reactions including anaphylaxis have been reported; donidalorsen can cause reductions in platelet count and increases in liver enzymes, although severe thrombocytopenia (<50,000/mm3) was not observed in the reported studies.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Donidalorsen for HAE: 81% Lower Attack Rate

Direct Clinical Takeaway & Evidence Summary

FDA Approves Donidalorsen for HAE: 81% Lower Attack Rate

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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