Ionis reports two-year OASISplus data showing 95% HAE attack reduction with DAWNZERA and sustained results following eight-week dosing.
Written By: Neha Vishwakarma, PharmD
Reviewed By: Pharmacally Editorial Team
Ionis Pharmaceuticals reported two-year data for DAWNZERA (donidalorsen), demonstrating sustained reductions in hereditary angioedema (HAE) attack rates in patients receiving long-term prophylactic treatment. The findings, announced on November 12, 2026, will be presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2026 Annual Scientific Meeting in Phoenix, Arizona. The results come from the open-label extension (OLE) and switch cohorts of the Phase 3 OASISplus study.
Patients continuing DAWNZERA treatment in the OLE cohort achieved a 95% overall reduction in HAE attack rates from baseline after two years. Patients who switched from other long-term prophylactic therapies maintained a 71% reduction relative to their previous treatment baseline. The findings also showed sustained attack reduction among patients receiving DAWNZERA every eight weeks (Q8W), alongside a favorable long-term safety profile.
Two-Year Efficacy Findings from OASISplus
The OASISplus OLE cohort included adult and adolescent patients continuing from the Phase 3 OASIS-HAE pivotal trial. Patients received DAWNZERA every four weeks (Q4W) or every eight weeks (Q8W).
After two years, 84% of patients remained in the OLE cohort. Across both dosing groups, the 83 patients included in the reported analysis achieved a 95% overall reduction in HAE attack rates from baseline. The findings indicate that the reduction in attack frequency observed during earlier treatment was sustained over the longer follow-up period.
The separate switch cohort evaluated patients previously receiving lanadelumab, C1-esterase inhibitor or berotralstat who transitioned to DAWNZERA according to a predefined protocol. After two years, 80% of patients remained in the cohort. Among the 64 patients included in the reported analysis, HAE attack rates were reduced by 71% compared with baseline while receiving their previous long-term prophylactic therapy.
The switch-cohort findings provide additional evidence of sustained attack reduction following a transition to DAWNZERA. However, the comparison was based on patients’ previous treatment baseline and was not a randomized head-to-head evaluation against the earlier prophylactic medicines.
Eight-Week Dosing and Treatment Burden
Ionis also reported a post hoc analysis examining patients eligible for Q8W dosing across the OASISplus OLE and switch cohorts. Patients who received DAWNZERA every eight weeks at the start of the OLE maintained a 95% overall reduction in HAE attack rates over two years, consistent with the reported findings for patients receiving Q4W dosing.
These results are relevant because less frequent administration could reduce treatment burden for people requiring long-term HAE prophylaxis. However, the post hoc nature of the analysis and the absence of a reported formal comparison between dosing schedules mean that the findings should not be interpreted as establishing equivalence or non-inferiority between Q4W and Q8W regimens.
Long-Term Safety and Tolerability
The long-term safety profile remained favorable, with no new safety signals observed. Most treatment-emergent adverse events were mild or moderate, and no serious treatment-emergent adverse events related to DAWNZERA were reported. The most common adverse reactions, occurring in at least 5% of treated patients, included injection-site reactions, upper respiratory tract infections, urinary tract infections and abdominal discomfort.
DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or its excipients. Hypersensitivity reactions, including anaphylaxis, have also been reported during treatment.
Clinical Context
DAWNZERA is an RNA-targeted medicine designed to reduce plasma prekallikrein (PKK), a protein involved in activating inflammatory mediators associated with acute HAE attacks. It is approved in the United States for prophylaxis to prevent HAE attacks in adults and pediatric patients aged 12 years and older.
HAE is a rare, potentially life-threatening genetic condition characterized by recurrent episodes of severe swelling affecting areas such as the face, extremities, abdomen and throat. The condition is estimated to affect approximately 7,000 people in the United States, making sustained attack prevention an important objective of long-term management.
Clinical Interpretation
The two-year OASISplus findings extend the results reported at ACAAI 2025, when the OLE cohort demonstrated a 94% mean attack-rate reduction at one year, while the switch cohort showed a 68% reduction relative to previous prophylactic treatment. The broadly consistent reductions at the two-year assessment support the durability of the observed treatment effect.
Nevertheless, the findings require cautious interpretation. OASISplus is an open-label, uncontrolled extension, with efficacy comparisons based on baseline rather than a concurrent placebo or active-treatment control. Patient retention of 84% in the OLE cohort and 80% in the switch cohort also makes the characteristics and outcomes of those who discontinued relevant to interpreting long-term results.
Furthermore, the Q8W findings arise from a post hoc analysis, while the switch-cohort results do not establish comparative superiority over previous prophylactic therapies. Detailed presentations, including confidence intervals, subgroup characteristics and discontinuation data, would help clarify the robustness and clinical applicability of these findings.
Overall, the two-year results strengthen the evidence for sustained HAE attack reduction with DAWNZERA and highlight the potential practical value of less frequent dosing. The extent to which these findings translate into comparative clinical benefits and reduced treatment burden will require further evaluation.
References
Ionis presents new long-term data supporting durable efficacy and disease control with DAWNZERA (donidalorsen) at ACAAI 2026 Annual Meeting, Ionis Pharmaceuticals, November 12, 2026.
A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE), ClinicalTrials.gov ID NCT05392114
About the Writer
Neha Vishwakarma (LinkedIn) is a Pharm.D professional with experience in clinical pharmacy, pharmacovigilance, and clinical research. She has hands-on experience in ADR assessment, ICSR processing, medication safety, and clinical data evaluation. Her research background in surgical site infections and antibiotic use supports her focus on evidence-based healthcare writing.