Slide 1: Cardiac Presentation and Treatment Response by Sex in Patients With Transthyretin Amyloidosis
Cardiac Presentation and Treatment Response by Sex in Patients With Transthyretin Amyloidosis: Pooled Analysis of Vutrisiran and Patisiran Phase 3 Studies M. Fontana1, S. Cuddy2, A. Gonzalez-Duarte3,4, S. K. Schwarting5,6, H. Mathelier7, N. Sarswat8, L. K. Stern9, R. Eiros10, T. Ishizu11, M. Zhang12
Slide 2: Study Rationale and Design
Study Rationale and Design Background Methods • ATTR, a progressive disease caused by deposition of misfolded • Analysis of pooled data from 203 females and 1199 males who TTR fibrils in the heart, peripheral nerves and other organs, received vutrisiran, patisiran, or placebo in phase 3 studies10–14
Slide 3: Baseline Characteristics of Female vs Male Patients With ATTR
Baseline Characteristics of Female vs Male Patients With ATTR ATTR-CM ATTRv-PN HELIOS-B APOLLO-B HELIOS-A APOLLO Characteristics Female Male Female Male Female Male Female Male P valueb n=49 n=605 n=38 n=321 n=58 n=106 n=58 n=167 Age, years, mean (SD) 73.7 (9.5) 75.5 (6.5) 75.9 (7.7) 74.6 (7.1) 57.2
Slide 4: Statistically Significant Differences Were Observed Between Sexes at Baseline
Statistically Significant Differences Were Observed Between Sexes at Baseline • Females exhibited: – Worse % predicted 6-MWT distance, showing worse functional capacity vs males (P<0.0001) – Lower KCCQ-OS score, indicating worse health status and QoL vs males (P=0.0029) – Higher E/e′ ratio, indicati
Slide 5: RNAi Therapeutics Reduced the Risk of All-Cause Mortality and All-Cause Hospitalisation vs Placebo
RNAi Therapeutics Reduced the Risk of All-Cause Mortality and All-Cause Hospitalisation vs Placebo in Females and Males with ATTR Results were consistent across individual studies and pooled analyses, without significant treatment-by-sex interaction All-Cause Mortalitya All-Cause Hospitalisation aIn
Slide 6: Consistent Benefits with RNAi Therapeutics vs Placebo in NT-proBNP, Functional Capacity, Health Status and Quality of Life
Consistent Benefits with RNAi Therapeutics vs Placebo in NT-proBNP, Functional Capacity, Health Status and Quality of Life in Females and Males with ATTR Results were consistent across individual studies and pooled analyses, without significant treatment-by-sex interaction NT-proBNP 6-MWT KCCQ-OS Th
Slide 7: Impact of RNAi Therapeutics on Cardiac Structure and Function was Consistent Between Females and Males
Impact of RNAi Therapeutics on Cardiac Structure and Function was Consistent Between Females and Males With ATTR Non-significant interaction P values for all measures show lack of notable treatment-by-sex interaction LVWT Average E/e′ Ratio GLS LVEF The treatment effect on the annual rate of change
Slide 8: Conclusions
Conclusions • The results of this pooled analysis of phase 3 clinical studies support the presence of sex-specific differences across the ATTR disease continuum of cardiomyopathy and polyneuropathy phenotypes • Across the ATTR spectrum, females exhibited a distinct baseline phenotype vs males, chara