Donidalorsen shows sustained benefit after HAE prophylaxis switch

Switching to donidalorsen from established long-term prophylaxis was associated with sustained reductions in hereditary angioedema (HAE) attack rates and improved quality of life over 1 year, according to results from the ongoing phase 3 OASISplus study.¹ The findings provide longer-term data on treatment transitions, an area of clinical uncertainty given high discontinuation rates with existing prophylactic therapies.

Investigators reported that patients who transitioned directly from lanadelumab, berotralstat, or C1 inhibitor (C1INH) replacement therapy experienced fewer attacks without a signal for worsening disease control during the switch. These results may help inform treatment sequencing decisions in adolescents and adults with HAE requiring prophylaxis, reducing attacks that may impact a patient’s career and education.²

“Results from a prespecified 16-week interim analysis of the OASISplus Switch cohort were previously reported and showed a reduction in overall HAE attacks with no overall mean increase in attacks during the switch and acceptable safety during the transition to donidalorsen,” wrote investigators.¹

Open-label extension evaluates switching from prior prophylaxis

OASISplus is a global, open-label phase 3 study evaluating donidalorsen, a prekallikrein-directed antisense oligonucleotide, in patients 12 years and older with HAE because of C1INH deficiency or dysfunction. The current analysis focused on the Switch cohort, which included patients who transitioned directly from prior long-term prophylaxis without a washout period.

A total of 64 patients received at least 1 dose of donidalorsen 80 mg administered subcutaneously every 4 weeks, and 83.1% completed 1 year of treatment. Prior therapies included lanadelumab in 31 patients, berotralstat in 11, and C1INH in 22. The mean age was 42 years, and 59.4% of participants were female.

The primary end point was safety, assessed by treatment-emergent adverse events (TEAEs). Secondary end points included monthly HAE attack rates and patient-reported outcomes such as the Angioedema Quality of Life (AE-QoL) score.

Sustained reductions in HAE attacks and improved QoL

At 1 year, the mean monthly HAE attack rate decreased by 67.6%, from 0.85 at baseline on prior prophylaxis to 0.28 during donidalorsen treatment. Reductions were observed across prior treatment groups, including 63.9% for lanadelumab, 83.1% for berotralstat, and 50.7% for C1INH.

Improvements were also seen in patients with both poorly controlled and well-controlled disease at baseline. Among those with poor control, attack rates declined by 68.1% over the treatment period.

Patient-reported outcomes supported these findings. The AE-QoL score improved by a mean of 12.2 points, exceeding the threshold for clinically meaningful change. Disease control, measured by the Angioedema Control Test, improved to well-controlled status in 90.4% of patients at week 52, vs 67.3% at baseline.

Treatment satisfaction also increased. Global satisfaction scores on the Treatment Satisfaction Questionnaire for Medication rose from 75.7 to 89.4 over 1 year, with gains in perceived effectiveness and convenience.

Safety findings were consistent with prior studies. TEAEs occurred in 87.5% of patients, most of which were mild or moderate. Common events included upper respiratory tract infection, nasopharyngitis, headache, and injection-site reactions. One serious adverse event was reported and was considered unrelated to treatment.

Clinical context and considerations for switching

Long-term prophylaxis is central to HAE management, as recurrent attacks can be unpredictable and potentially life-threatening. Available options, including monoclonal antibodies, oral kallikrein inhibitors, and C1INH replacement, have demonstrated efficacy but are associated with adherence challenges and discontinuation rates approaching 45% to 55% in real-world analyses.

The current findings suggest that switching among prophylactic classes may be feasible without loss of disease control when guided by pharmacokinetic considerations. Investigators used a prespecified algorithm to overlap therapies based on half-life, which may have contributed to the absence of increased attacks during transition.

“These long-term results provide a promising foundation to create an evidence-based framework and process for clinicians to manage a patient’s transition between treatment options for HAE,” wrote investigators.

References

1. Reidl MA, Bernstein JA, Jacobs JS, et al. Switching long-term prophylaxis to donidalorsen for hereditary angioedema: 1-year OASISplus results. Allergy. Published online March 14, 2026. doi:10.1111/all.70294
2. Bork K, Anderson JT, Caballero T, et al. Assessment and management of disease burden and quality of life in patients with hereditary angioedema: a consensus report. Allergy Asthma Clin Immunol. 2021;17(1):40. doi:10.1186/s13223-021-00537-2