D3.444 - Efficacy and Safety of Donidalorsen for Patients With Hereditary Angioedema in Europe Who Switched From Prior Long-Term Prophylaxis: Results From the OASISplus Study

Donidalorsen is a prekallikrein-directed antisense oligonucleotide approved in the US for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and paediatric patients ≥12 years of age. In the ongoing global OASISplus study (NCT05392114), patients on stable doses of a long-term prophylactic treatment (LTP) switched without washout to donidalorsen once every 4 weeks (Q4W) for 52 weeks (Switch cohort). Donidalorsen had an acceptable safety profile and improved HAE attack rates in the global population over Weeks 0 to 52. Here, one-year efficacy and safety results for donidalorsen in the European subgroup of the Switch cohort are reported.

The OASISplus study included patients located in 9 European countries. Patients received their prior LTP (lanadelumab, berotralstat, or C1 inhibitor [C1INH]) through the 10-week baseline screening period, then switched, without washout, to donidalorsen 80 mg administered subcutaneously Q4W for 52 weeks, according to a predefined algorithm. Endpoints included here are the incidence and severity of treatment-emergent adverse events (TEAEs) and the rate of monthly HAE attacks from baseline to Week 52.

Of the 21 patients in the Switch cohort who received donidalorsen in Europe, 17 (81%) patients completed 1 year of the study; most were White (95%), and the mean (standard deviation) age was 47 (10) years. Fifteen (71%) patients in Europe reported TEAEs (14 [67%] reported mild or moderate TEAEs), and 8 (38%) reported TEAEs considered to be related to the study drug. The most common TEAEs were headache, injection-site erythema, and nasopharyngitis. The overall reduction in mean HAE attack rate was 75% from the baseline period (on prior LTP) through the treatment period (Weeks 0 to 52) on donidalorsen (Figure 1). The reduction in HAE attack rate during this period was 65% in patients on prior lanadelumab, 85% in patients on prior berotralstat, and 57% in patients on prior C1INH treatment.

Donidalorsen had an acceptable safety profile and led to sustained reductions in HAE attack rate in the European subgroup of the OASISplus Switch cohort, consistent with results from the global population. These results from patients with HAE in Europe support the viability of switching from prior LTPs to donidalorsen.