Medicine

Donidalorsen Taken Every Eight Weeks Is Safe And Has Durable Efficacy In Reducing Attack Rates In Hereditary Angioedema: Study

• byDoctor News Daily Team
• 18 February, 2025
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USA: A previous phase 2 open-label extension (OLE) study of donidalorsen in patients with Type 1/2 hereditary angioedema (HAE) showed a 76% reduction in monthly attack rate and improved quality-of-life (QoL) with every eight weeks (Q8W) dosing at Year 1.

A recent article published in The Journal of Allergy and Clinical Immunology reports the Year 2 results of patients who received donidalorsen Q8W.

Michael Manning, Allergy, Asthma & Immunology Associates, and colleagues reported that at Year 2, donidalorsen Q8W was well-tolerated, had plasma prekallikrein levels similar to Q4W dosing, and showed durable efficacy in hereditary angioedema attack reduction. The findings supported the continued study of Q8W dosing.
Hereditary angioedema is an inherited condition with characteristics of recurrent episodes of nonpitting, nonpruritic, subcutaneous or submucosal swelling without urticarial lesions. Multiple body areas, including feet, hands, genitalia, intestinal wall, face, larynx, or tongue, can be involved.
There exist two main types of HAE that are inherited in an autosomal dominant manner. Type I HAE accounts for about 85% of cases and results from a quantitative deficiency of C1 inhibitor. Type II HAE is responsible for about 15% of cases and results from a dysfunctional C1 inhibitor protein. Donidalorsen is an investigational ligand-conjugated antisense oligonucleotide designed for hepatic uptake and inhibition of prekallikrein production.
Dr. Manning and the team presented the two-year update on the impact of donidalorsen taken every 8 weeks in patients with HAE.
The OLE study had fixed (Weeks 1–16, donidalorsen 80 mg subcutaneously every 4 weeks [Q4W]) and flexible (Weeks 17–105, donidalorsen 80 mg Q4W, 80 mg Q8W, or 100 mg Q4W) dosing periods.
Based on the analysis, the researchers reported the following findings:
Eight of 17 patients received donidalorsen Q8W; 5 patients remained attack-free, and 3 patients returned to Q4W by Year 2.
63% of patients reported a treatment-emergent adverse event (TEAE); only 1 patient reported a possible study drug-related TEAE (abdominal pain).
The mean monthly attack rate across all 8 patients was 0.04 at Year 2 compared with 0.28 at Year 1, an 83% reduction from baseline (randomized study run-in rate, 2.70).
The mean percent change in plasma prekallikrein at Year 2 was similar for patients receiving Q8W (–59.1) and Q4W (–54.3) dosing.
Year 2 (27.4) and Year 1 (25.0) improvement in mean Angioedema QoL total scores were comparable.
"At Year 2, donidalorsen Q8W was well-tolerated, had plasma prekallikrein levels comparable to Q4W dosing, and showed durable efficacy in HAE attack reduction, supporting the continued study of Q8W dosing," the researchers wrote.
Reference:
DOI: https://doi.org/10.1016/j.jaci.2023.11.031