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Título

Primary Results from Post Hoc Analysis of the APOLLO-B Brazilian Subpopulation, A Phase 3 Study of Patisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy

Resumo

Background: Transthyretin amyloidosis (ATTR) is a progressive, fatal disease caused by toxic misfolded transthyretin (TTR) amyloid deposits. Patisiran, an RNA interference therapeutic, inhibits synthesis of wild-type and variant TTR and is approved for the treatment of hereditary ATTR with polyneuropathy.

Objective: Describe efficacy and safety of patisiran in patients from Brazil with ATTR cardiomyopathy (ATTR-CM) via a post hoc subgroup analysis of the global APOLLO-B study (NCT03997383).

Methods: Patients 18–85 years of age with ATTR-CM and heart failure were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. Primary endpoint was change from baseline (CFB) in functional capacity (6-minute walk test) at Month 12 for patisiran vs placebo. Secondary endpoints included CFB to Month 12 in health status and quality of life (Kansas City Cardiomyopathy Questionnaire-Overall Summary [KCCQ-OS]). Exploratory endpoints included CFB in cardiac biomarkers and Perugini grade by Tc-99m scintigraphy, the latter assessed in a subset of patients in an imaging study within APOLLO-B.

Results: Of 360 patients in APOLLO-B, 42 were from Brazil (patisiran, n=20; placebo, n=22): median (range) age at screening, 73 (51, 85) years; male, 81%; wild-type ATTR, 54.8%. No patients were receiving tafamidis at baseline. Patisiran showed benefit vs placebo in 6-minute walk test (median [95% CI] CFB [meters]: −2.02 [−58.5, 42.9] vs −30.1 [−72.2, 3.5]; Hodges-Lehmann estimate of median difference [95% CI]: 31.4 [−16.6, 79.4]; Figure 1A) and in KCCQ-OS (least squares mean [SEM] CFB: 9.4 [3.8] vs 2.6 [3.7]; least squares mean difference [SEM]: 6.8 [5.3]; Figure 1B). Death was reported in 0 patisiran patients vs 3 (13.6%) placebo. The ratio of adjusted geometric mean fold-change (patisiran:placebo [95% CI]) was 0.77 (0.57, 1.03) for NT-proBNP and 0.87 (0.68, 1.12) for troponin I. In the imaging subset (n=35), 11/18 (61.1%) patisiran patients improved Perugini grade vs 0/10 placebo at Month 12 (Figure 2). Few patisiran patients experienced serious (8 [40%]) or severe (4 [20%]) adverse events; none were drug related.

Conclusion: In Brazilian patients with ATTR-CM, potential benefit was observed with patisiran on functional capacity, health status and quality of life, cardiac biomarkers, and Perugini grade, consistent with data from the global APOLLO-B population. The results are descriptive; the study was not powered to detect treatment effects specific to this subgroup.

Palavras Chave

Transthyretin amyloidosis; cardiomyopathy; Patisiran

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