D3.441 - Switching to Donidalorsen for Hereditary Angioedema: 1-Year Results From the Phase 3 OASISplus Study

Donidalorsen is a prekallikrein-directed antisense oligonucleotide indicated in the US for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and paediatric patients ≥12 years of age. In the phase 3, placebo-controlled OASIS-HAE study (NCT05139810), donidalorsen significantly reduced monthly HAE attack rate and was well tolerated. Here, we report 1-year safety and efficacy data from patients who opted to switch from long-term prophylactic treatments (LTPs) to donidalorsen in the OASISplus study (NCT05392114).

Patients with HAE on stable doses (≥12 weeks) of lanadelumab, subcutaneous (SC) or intravenous C1 inhibitor (C1INH), or berotralstat switched to 80 mg donidalorsen SC once every 4 weeks without washout using a predefined algorithm. The primary endpoint was incidence and severity of treatment-emergent adverse events (TEAEs). Other endpoints included monthly HAE attack rate, the percentage of days attack free, Angioedema Quality of Life (AE-QoL), and well-controlled disease on the Angioedema Control Test (score ≥10) at Week 52, as well as prekallikrein concentration at Week 48.

Sixty-five patients switched from lanadelumab (n = 32), C1INH (n = 22), or berotralstat (n = 11) to donidalorsen; 64 (98%) received ≥1 dose, and 54 (83%) completed 1 year of treatment. Median exposure was 392 days. Fifty-six (88%) patients reported TEAEs (51 [80%] reported mild-to-moderate TEAEs); the most common TEAEs were upper respiratory tract infection (23%), nasopharyngitis (19%), and injection-site erythema (16%). Twenty-four (38%) patients experienced treatment-related TEAEs; 1 discontinued treatment due to a non–treatment-related serious adverse event. From baseline (on prior therapy) to the on-treatment period (Weeks 0–52), mean HAE attack rate decreased by 68%. From Weeks 4 to 52, patients were attack free for a mean of 99% of days, with a median longest attack-free interval of 215 days. Mean AE-QoL total scores improved by 12.2 points from baseline to Week 52. The percentage of patients reporting well-controlled disease increased from 64% (baseline) to 90% (Week 52). There was a mean 74% decrease in plasma prekallikrein concentrations from baseline to Week 48.

Donidalorsen was generally well tolerated by patients switching from prior LTPs. Improvements in HAE attack rate, quality of life, and disease control were sustained through 1 year.