Long-Term Impact of Vutrisiran in Patients With TTR Amyloidosis With Cardiomyopathy: 1-Year Efficacy and Safety Outcomes From the HELIOS-B Open-Label Extension

BACKGROUND: In HELIOS-B (A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), vutrisiran reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular events and slowed disease progression measures versus placebo in patients with TTR (transthyretin) amyloidosis with cardiomyopathy after 33 to 36 months. We report the long-term efficacy and safety of vutrisiran from an ongoing open-label extension of HELIOS-B. METHODS: Patients who completed HELIOS-B could enroll in the open-label extension, continuing with vutrisiran 25 mg every 3 months (continuous vutrisiran) or, if previously receiving placebo, initiating vutrisiran 25 mg every 3 months (placebo/vutrisiran). Prespecified end points assessed in the open-label extension are the composite of ACM and cardiovascular events, ACM, Kansas City Cardiomyopathy Questionnaire–Overall Summary score, New York Heart Association class, and NT-proBNP (N-terminal pro–B-type natriuretic peptide) and troponin I levels. Outcomes were assessed through month 48 in this analysis. RESULTS: Of 654 participants in HELIOS-B (vutrisiran, n=326; placebo, n=328), 478 completed double-blind treatment and 466 (vutrisiran, n=243; placebo, n=223) entered the open-label extension. In the continuous vutrisiran group, the risk of first cardiovascular event or ACM was reduced by 37% (hazard ratio, 0.63 [95% CI, 0.51, 0.79]; P =0.0001) and ACM by 37% (hazard ratio, 0.63 [95% CI, 0.46, 0.84]; P =0.0023) versus the placebo/vutrisiran group. Through month 48, patients in the continuous vutrisiran group had preserved health status and quality of life per Kansas City Cardiomyopathy Questionnaire–Overall Summary score (least squares mean difference, 9.0 [95% CI, 5.3, 12.6]; P <0.0001) and more patients had improved or stable New York Heart Association class (odds ratio, 1.6 [95% CI, 1.1, 2.2]; P =0.0084) versus the placebo/vutrisiran group. Benefits in the continuous vutrisiran group were maintained for NT-proBNP and troponin I levels (adjusted geometric mean fold change ratios, 0.66 [95% CI, 0.58, 0.74]; P <0.0001; and 0.71 [95% CI, 0.64, 0.79]; P <0.0001, respectively) versus the placebo/vutrisiran group. Similar benefits were observed in the vutrisiran monotherapy population. No new safety signals were observed. CONCLUSIONS: Long-term vutrisiran resulted in clinically meaningful benefits across mortality, cardiovascular events, cardiac biomarkers, functional status, and quality of life in patients with TTR amyloidosis with cardiomyopathy through month 48. Patients initially treated with vutrisiran had better outcomes than those first receiving placebo, highlighting the importance of early diagnosis and treatment in TTR amyloidosis with cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04153149.