D3.440 - Long-Term Efficacy and Safety of Donidalorsen for Hereditary Angioedema Among Patients in Europe: A Regional Analysis of the OASISplus Study

In the global, long-term open-label extension (OLE) cohort of the phase 3 OASISplus study (NCT05392114), donidalorsen, a prekallikrein-directed antisense oligonucleotide, reduced hereditary angioedema (HAE) attacks and had an acceptable safety profile after 1 year of treatment. In this post hoc analysis, we evaluated the safety and efficacy of donidalorsen in the European subgroup of the OLE cohort after 1 year.

The OASISplus study included patients with HAE across 9 European countries who rolled over from the pivotal phase 3 OASIS-HAE study (NCT05139810). Patients received donidalorsen 80 mg subcutaneously once every 4 weeks (Q4W) or 8 weeks (Q8W) for 52 weeks. Endpoints included HAE attack rate during Weeks 0 to 52 and Weeks 4 to 52 compared to OASIS-HAE baseline, patients who achieved attack-free status or a clinical response (≥70% reduction in HAE attacks) during Weeks 4 to 52, and incidence of treatment-emergent adverse events (TEAEs) during Weeks 0 to 52.

Of 43 patients who received donidalorsen in Europe, 40 (93%) completed 1 year of treatment. Two patients discontinued due to an adverse event (5%) and 1 withdrew voluntarily (2%), all in the Q4W group. Donidalorsen reduced the overall mean HAE attack rate by 96% from baseline (Q4W, 96%; Q8W, 94%) during the 1-year on-treatment period (Figure); results were similar from baseline to Weeks 4 to 52: Q4W, 97%; Q8W, 95%. In Europe, all patients in the Q4W and Q8W groups achieved a ≥70% reduction in HAE attack rate from baseline during Weeks 4 to 52. Additionally, 59% of patients in the Q4W group and 33% in the Q8W group achieved attack-free status during this period. Most TEAEs in European patients were mild or moderate in severity. TEAEs were reported in a total of 41 (95%) patients; 13 (30%) had TEAEs considered related to donidalorsen. Serious TEAEs were reported in 4 (9%) patients; none were deemed related to donidalorsen. The most common TEAE was nasopharyngitis in 12 (28%) patients. One death (suicide) occurred in the Q4W group and was deemed not related to donidalorsen.

The efficacy and safety of donidalorsen in patients in the European subgroup of the OASISplus OLE cohort were comparable to those in the overall population. In Europe, donidalorsen reduced overall mean HAE attack rate, all patients achieved a ≥70% reduction in HAE attack rate, and most TEAEs were mild or moderate in severity. These results support the use of donidalorsen for patients with HAE in Europe.