D3.439 - Donidalorsen For The Treatment Of Hereditary Angioedema: 1-Year Results From The OASISplus Open-Label Extension Cohort

Hereditary angioedema (HAE) is a rare disease characterised by recurrent, potentially life-threatening episodes of tissue swelling. Donidalorsen is a prekallikrein-directed antisense oligonucleotide approved in the US for prophylaxis to prevent attacks of HAE in adult and paediatric patients ≥12 years of age. Long-term results from the open-label extension (OLE) cohort of the ongoing OASISplus study (NCT05392114) of donidalorsen are reported.

OASISplus included a cohort of patients who rolled over from the phase 3 OASIS-HAE study (NCT05139810). Patients who received donidalorsen 80 mg subcutaneously every 4 weeks (Q4W) or placebo either Q4W or every 8 weeks (Q8W) in OASIS-HAE received donidalorsen Q4W in OASISplus. Patients who received donidalorsen Q8W in OASIS-HAE continued Q8W dosing or received donidalorsen Q4W if they were not attack-free for ≥8 weeks. The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included the rate of HAE attacks/month and Angioedema Quality of Life (AE-QoL). Plasma prekallikrein concentration was an exploratory endpoint. Results are from a prespecified 1-year descriptive analysis.

The OLE cohort included 83 patients (Q4W, n=69 [83%]; Q8W, n=14 [17%]), of whom 75 (90%) completed through Week 52. Eight patients (9.6%) terminated treatment early, 3 (3.6%) due to TEAEs (2 [2.4%] were treatment-related). Median exposure to donidalorsen was 392.3 days. Sixty-four (Q4W, 93%) and 11 (Q8W, 79%) patients reported TEAEs that were mostly of mild-to-moderate severity and non–treatment-related. The most common treatment-related TEAE was injection-site discoloration (6%). At Week 52, the mean HAE attack rate from OASIS-HAE baseline decreased by 94% (Q4W) and 95% (Q8W, Figure). The overall mean longest attack-free interval was 267 days, and 63 (76%) patients were attack-free for 6 consecutive months from Weeks 4–52. There was an overall mean 90% decrease in the rate of HAE attacks involving the abdomen and a 97% decrease in HAE attacks involving the larynx or periphery. Patients reported clinically meaningful (≥6-point) improvements in mean AE-QoL total score (Q4W, 28.1 points; Q8W, 26.7 points). Mean prekallikrein concentrations decreased by 77% (Q4W) and 50% (Q8W) at Week 52.

Donidalorsen had an acceptable safety and tolerability profile and improved HAE attack rate, regardless of anatomical location, and patient-reported QoL at 1 year.