Background: Donidalorsen, a prekallikrein-directed antisense oligonucleotide indicated for prophylaxis of hereditary angioedema (HAE) attacks in patients aged ≥ 12 years, demonstrated efficacy and acceptable safety in the phase 3, placebo-controlled OASIS-HAE trial (NCT05139810). Here, we report 1-year results from the corresponding open-label extension (OLE) cohort of the OASISplus study (NCT05392114). Methods: OASISplus included patients who rolled over from OASIS-HAE. Patients who received donidalorsen 80 mg or placebo subcutaneously every 4 weeks (Q4W) in OASIS-HAE received donidalorsen Q4W in OASISplus. Patients who received donidalorsen 80 mg or placebo every 8 weeks (Q8W) in OASIS-HAE received donidalorsen Q8W or Q4W, if not attack-free in the final 8 weeks of OASIS-HAE. The primary endpoint was safety (ie, incidence of treatment-emergent adverse events TEAEs). Secondary endpoints included the monthly rate of HAE attacks and Angioedema Quality of Life (AE-QoL). Results: The OLE cohort included 83 patients (Q4W, n=69 83%; Q8W, n=14 17%). Of these, 75 (90.4%) completed Year 1, and 6 patients receiving donidalorsen Q8W in OASIS-HAE switched to the Q4W dosing group in the OLE. Median donidalorsen exposure was 392.3 days. From Weeks 0 to 52, reductions in mean HAE attack rate from OASIS-HAE baseline were 94% (Q4W) and 95% (Q8W), and patients reported clinically meaningful improvements in mean AE-QoL total score at Week 52 (Q4W, 28.1 points; Q8W, 26.7 points). Twenty-two (27%) patients reported treatment-related TEAEs; none were serious, and injection-site reactions were the most frequently reported. Conclusion: Donidalorsen demonstrated sustained reductions in HAE attack rate, improvements in QoL, and an acceptable safety profile after 1 year of treatment. Keywords: disease control, donidalorsen, hereditary angioedema, open-label, phase 3
Lumry et al. (Sun,) studied this question.