Dados do Trabalho

Título

Effect of Patisiran Treatment in patients with hATTR amyloidosis with cardiomyopathy and polyneuropathy: post-hoc analysis of the APOLLO-B study.

Introdução e/ou Fundamento

Most patients with hereditary ATTR (hATTR) amyloidosis develop a mixed phenotype of cardiomyopathy (CM) and polyneuropathy (PN). Patisiran, an RNAi therapeutic that inhibits synthesis of TTR, was approved for the treatment of hATTR-PN amyloidosis. The APOLLO-B study (NCT03997383) demonstrated the clinical efficacy of patisiran in patients with ATTR-CM amyloidosis.

Objetivo

Describe the clinical efficacy of patisiran in patients with hATTR amyloidosis and a mixed phenotype in APOLLO-B.

Materiais e Métodos

In APOLLO-B, patients with ATTR amyloidosis with CM were randomized (1:1) to patisiran IV 0.3 mg/kg or placebo Q3W for 12 months. The primary endpoint was change from baseline in 6-MWT (functional capacity) at Month 12 (M12) with patisiran vs placebo. Secondary and exploratory endpoints included health status and quality of life (KCCQ-OS), cardiac biomarkers (NT-proBNP, troponin I), and scintigraphy (Perugini grade). Mixed phenotype patients in this analysis had hATTR amyloidosis AND one of the following without a known cause of PN unrelated to hATTR amyloidosis: (1) history of PN, (2) PND score ≥I, (3) Norfolk QOL-DN score ≥30, or (4) plasma neurofilament light chain level greater than the upper limit reference value established by Mayo Clinic laboratories.

Resultados

Mixed phenotype group included 59 patients (patisiran, n=31; placebo, n=28; NYHA class ≥II, 91.5%; PND II, 22.0%; V122I variant, 42.4%). In this group, patisiran reduced serum TTR attaining a mean (SD) percent reduction of 85.3% (13.39) at M12. A benefit in 6-MWT was observed with patisiran treatment vs placebo at M12 (median [95% CI] change from baseline: -10.42 [-58.50, 10.62] [patisiran]; -17.97 [-52.35, 9.86] [placebo]). Patisiran showed benefit in KCCQ-OS at Month 6 and continuing through M12 (mean [SEM] change from baseline at M12: 3.86 [4.16] [patisiran]; -2.25 (3.79) [placebo]). Patisiran showed favourable trends in change from baseline of NT-proBNP (geometric mean fold change [95% CI]: 1.09 [0.90, 1.31] [patisiran]; 1.33 [1.12, 1.57] [placebo]) and troponin I (geometric mean fold change [95% CI]: 1.10 [0.96, 1.25] [patisiran]; 1.33 [1.14, 1.55] [placebo]) at M12 vs placebo. Imaging assessments at M12 supported the benefit of patisiran; Perugini grade reduced from baseline in 53.8% (7/13) of evaluable patisiran patients vs no change from baseline in 100% (7/7) of evaluable placebo patients.

Conclusões

In APOLLO-B, assessments demonstrated benefits of patisiran on functional capacity, health status and quality of life, as well as a trend towards benefit in cardiac biomarkers at M12 vs placebo. This post-hoc analysis showed consistent results with the overall APOLLO-B population, supporting the benefit of patisiran vs placebo in patients with hATTR amyloidosis and a mixed phenotype.