Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis

J Cardiovasc Transl Res. 2013 Dec;6(6):1011-20. doi: 10.1007/s12265-013-9512-x. Epub 2013 Oct 8.

Abstract

This phase II, open-label, single-treatment arm study evaluated the pharmacodynamics, efficacy, and safety of tafamidis in patients with non-Val30Met transthyretin (TTR) amyloidosis. Twenty-one patients with eight different non-Val30Met mutations received 20 mg QD of tafamidis meglumine for 12 months. The primary outcome, TTR stabilization at Week 6, was achieved in 18 (94.7%) of 19 patients with evaluable data. TTR was stabilized in 100% of patients with non-missing data at Months 6 (n = 18) and 12 (n = 17). Exploratory efficacy measures demonstrated some worsening of neurological function. However, health-related quality of life, cardiac biomarker N-terminal pro-hormone brain natriuretic peptide, echocardiographic parameters, and modified body mass index did not demonstrate clinically relevant worsening during the 12 months of treatment. Tafamidis was well tolerated. In conclusion, our findings suggest that tafamidis 20 mg QD effectively stabilized TTR associated with several non-Val30Met variants.

Trial registration: ClinicalTrials.gov NCT00630864.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyloid / genetics*
  • Amyloid Neuropathies, Familial / diagnosis
  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / physiopathology
  • Benzoxazoles / adverse effects
  • Benzoxazoles / therapeutic use*
  • Disease Progression
  • Europe
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Prealbumin / genetics*
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Amyloid
  • Benzoxazoles
  • Prealbumin
  • amyloid prealbumin
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT00630864