Primary Results From APOLLO-B Open -label Extension Study Of Patisiran In Patients With Transthyretin Cardiac Amyloidosis

Abstract Introduction The Phase 3, placebo–controlled APOLLO–B study (NCT03997383) is evaluating the efficacy and safety of patisiran in patients (pts) with ATTR cardiac amyloidosis in a 12–month (M) double–blind (DB) period followed by an open–label extension (OLE) period when all pts receive patisiran. During the DB period, patisiran demonstrated statistically significant differences vs placebo in change from baseline (CFB) to M12 in 6–minute walk test (6MWT) and KCCQ–OS, and nominal significance in NT–proBNP and troponin I. Patisiran preserved functional capacity, health status and quality of life (QoL), while placebo was associated with steady worsening. Here, we describe data of the APOLLO–B OLE period. Methods Eligible pts (18–85 yrs) had echocardiographic evidence of cardiac amyloidosis and either ATTR amyloid detected in tissue biopsy or diagnosed by nonbiopsy criteria. Medical history of heart failure (HF) due to ATTR amyloidosis with ≥1 prior HF hospitalization or current clinical evidence of HF was required. Pts were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12M. All pts completing the 12M DB period were eligible to receive patisiran in the OLE for up to 36M. Assessments in the OLE include CFB in 6MWT, KCCQ–OS, NT–proBNP, and troponin I, among other endpoints. Results At baseline, 359 pts (placebo, n=178; patisiran, n=181) received study drug in DB period: median (range) age, 76.0 (41, 85) yrs; male, 89%; wtATTR, 80%; receiving tafamidis, 25%. Of these, 334 (93%) pts entered the OLE. Preliminary data show that CFB to M18 in the patisiran arm were similar to results at M12 for 6MWT, KCCQ–OS, NT–proBNP, and troponin I. In the placebo arm, patisiran initiation was associated with a slower rate of worsening (6MWT) or relative stability (KCCQ–OS, NT–proBNP, troponin I) in each endpoint from M12 to M18 vs DB period. Differences between patisiran and placebo groups at M12 persisted at M18 (Table). Patisiran demonstrated an acceptable safety profile with no new safety concerns. Conclusions Preservation of functional capacity, health status and QoL by patisiran has been observed to date to be sustained through 18M of treatment in pts with ATTR cardiac amyloidosis. Placebo–treated pts initiating patisiran at M12 appear to show stabilization in these endpoints at M18. Early treatment initiation is important, as differences across evaluated endpoints persisted between patisiran and placebo arms after placebo–treated pts initiated patisiran.