The purpose of this study is to evaluate the efficacy and safety of patisiran in
participants with ATTR amyloidosis with cardiomyopathy.

APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

Transthyretin Amyloidosis (ATTR)

Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

Patisiran

Clinical Trial Site

APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

Distance in meters walked in 6 minutes, longer distances indicate greater functional
capacity. Missing 6MWT values due to non-COVID-19 death or inability to walk due to ATTR
disease progression were imputed using the worst 10th percentile change observed in the
DB period. Missing 6-MWT values due to other reasons are multiply imputed to create 100
complete datasets. The change from baseline is averaged across the 100 complete datasets.

The KCCQ is a 23-item self-administered questionnaire quantifying 6 domains (symptoms,
physical function, quality of life, social limitation, self-efficacy, and symptom
stability) and 2 summary scores (clinical and overall summary [OS]). Scores are
transformed to a range of 0-100, in which higher scores reflect better health status.

The composite endpoint was analyzed using the stratified win ratio method, stratified by
baseline tafamidis use. This method combines all-cause mortality, frequency of CV events
(CV hospitalizations and HF visits) and change from baseline in 6-MWT in a hierarchical
fashion. This method makes within-stratum pairwise comparisons for all patisiran-placebo
participant pairs in a sequential manner (first mortality, then CV events, then 6-MWT),
with later steps evaluated only in the case of a tie on the prior step. Within each
stratum, the win ratio is the total number of 'winners' divided by the total number of
'losers' in the active group. A win ratio >1 represents a favorable outcome for
patisiran.

The hazard rate of all-cause mortality and all-cause hospitalizations and urgent HF
visits will be compared between treatment groups using an Andersen-Gill model. A hazard
ratio <1 represents a favorable outcome for patisiran.

The hazard rate of all-cause mortality and all-cause hospitalizations and urgent HF
visits was compared between treatment groups using a modified Andersen-Gill model. A
hazard ratio <1 represents a favorable outcome for patisiran.

Participants will be administered multiple doses of patisiran in the double-blind and
open-label extension period.

Participants will be administered multiple doses of placebo in the double-blind period.
In the open-label extension period, participants will be administered multiple doses of
patisiran.