Primary Results From Helios-B, a Phase 3 Study of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy

aBased on IPTW-adjusted Kaplan-Meier curves; bPrimary analysis based on the modified Andersen-Gill model, also known as LWYY; cTime to first event HR derived from Cox PH model, p-value derived from Log-rank test. Abbreviations: ACM, all-cause mortality; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; IPTW, inverse probability of treatment weighting; LWYY, Lin, Wei, Yang , and Ying [...] of Events Freedom From CV Events or ACM, % Placebo Vutrisiran Time to First CV Event or All-Cause Mortalitya 0 3 6 9 12 15 18 21 24 27 30 33 36 39 100 90 80 70 60 50 40 30 Follow-Up Time (Months) censored Primary analysisb: HR=0.718 (95% CI: 0.555, 0.929), p-value=0.0118 Time-to-firstc: HR=0.716 (95% CI: 0.566, 0.905), p-value=0.0062 Achieved 28% reduction in the overall population OVERALL POPULAT [...] Abbreviations: CI, confidence interval; CV, cardiovascular; DB, double-blind; HR, hazard ratio; LWYY, Lin, Wei, Yang , and Ying; PH, proportional hazard. [...] Abbreviations: CI, confidence interval; HR, hazard ratio; IPTW, inverse probability of treatment weighting; OLE, open label extension. [...] Abbreviations: ATTR, transthyretin amyloidosis; CI, confidence interval; CV, cardiovascular; hATTR, hereditary transthyretin amyloidosis; HR, hazard ratio; NT-proBNP, N-terminal prohormone of B-type natriuretic peptide; NYHA, New York Heart Association; wtATTR, wild-type transthyretin amyloidosis. 9 OVERALL POPULATION Subgroup Vutrisiran/Placebo HR 95% CI (N=654) <75 (N=257) ≥75 (N=397) No (N=395 [...] aBased on IPTW-adjusted Kaplan-Meier curves; bPrimary analysis based on the modified Andersen-Gill model, also known as LWYY; cTime to first event HR derived from Cox PH model, p-value derived from Log-rank test; dTime to all-cause mortality includes data from the double-blind period and up to 6 months in the OLE, deaths after end of study are included in the analysis, HR derived from Cox PH mod [...] Abbreviations: CI, confidence interval; CV, cardiovascular; HR, hazard ratio; IPTW, inverse probability of treatment weighting; LWYY, Lin, Wei, Yang , and Ying; PH, proportional hazard. [...] © The New England Journal of Medicine (2024)11 Evidence of Added Benefit on Top of Tafamidis censored Cox model HRd=0.588 (95% CI: 0.320, 1.081) Log-rank test p-value=0.0983 Time to All-Cause Mortalitya Placebo Vutrisiran Adjusted Survival Probability, % Favourable trends in baseline tafamidis subgroup on both primary composite (22% reduction) and all-cause mortality (41% reduction) TAFAMIDIS SUBG [...] aBased on IPTW-adjusted Kaplan-Meier curves; bPrimary analysis based on the modified Andersen-Gill model, also known as LWYY; cTime to first event HR derived from Cox PH model, p-value derived from Log-rank test; dTime to all-cause mortality includes data from the double-blind period and up to 6 months in the OLE, deaths after end of study are included in the analysis, HR derived from Cox PH mod [...] Abbreviations: CI, confidence interval; CV, cardiovascular; HR, hazard ratio; IPTW, inverse probability of treatment weighting; LWYY, Lin, Wei, Yang , and Ying; OLE, open-label extension; PH, proportional hazard.