Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Analyses From ATTR-ACT

Abstract

Objectives: Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis (ATTRv) and wild-type transthyretin (ATTRwt).

Background: ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt.

Methods: In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv.

Results: There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 [95% confidence interval (CI): 0.474 to 1.052]; p = 0.0875) and ATTRv (hazard ratio: 0.690 [95% CI: 0.408 to 1.167]; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019).

Conclusions: Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).

Keywords: clinical trial; hereditary; tafamidis; transthyretin amyloid cardiomyopathy; wild-type.

Conflict of interest statement

Funding Support and Author Disclosures Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual anonymized participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. This study was sponsored by Pfizer. Dr. Rapezzi has received unrestricted research grants and fees for advisory board meetings from Pfizer. Dr. Elliott has received consultancy fees from Pfizer and Alnylam. Dr. Damy has served on a scientific advisory board for Pfizer; has received funding from Pfizer for scientific meeting expenses; and his institution has received grant support from Pfizer. Dr. Nativi-Nicolau’s institution has received funding for clinical trials from Pfizer, Akcea, and Eidos; and has received educational grants from Pfizer. Dr. Nativi-Nicolau has been a consultant for Pfizer, Eidos, Akcea, and Alnylam. Dr. Berk has received consultancy fees from Alnylam Pharmaceutical, Akcea Therapeutics, Intellia Therapeutics, and Corino Therapeutics. Dr. Boman has served on scientific advisory boards for Pfizer; and has received funding for scientific meetings. Mr. Gundapaneni, Drs. Patterson and Sultan are employees of and hold stock options with Pfizer. At the time of this analysis, Dr. Schwartz was an employee of Pfizer; holds stock and stock options with Pfizer, and is now retired. Dr. Maurer has received grant support from the National Institutes of Health (HL HL139671-01, AG R21AG058348, and AG K24AG036778); his institution has received funding for clinical trials from Pfizer, Prothena, Eidos, and Alnylam; and he has received consulting income from Pfizer, GlaxoSmithKline, Eidos, Prothena, Akcea, and Alnylam. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.