Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy

Amyloid. 2016 Sep;23(3):178-183. doi: 10.1080/13506129.2016.1207163. Epub 2016 Aug 5.


Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind, placebo-controlled trial, and 1-year open-label extension study, with a second long-term open-label extension study ongoing. Subgroup analysis of the effectiveness of tafamidis in the pivotal study and its open-label extensions revealed a relatively cohesive cohort of patients with mild neuropathy (i.e. Neuropathy Impairment Score for Lower Limbs [NIS-LL] ≤ 10) at the start of active treatment. Early treatment with tafamidis for up to 5.5 years (≥1 dose of tafamidis meglumine 20 mg once daily during the original trial or after switching from placebo in its extension) resulted in sustained delay in neurologic progression and long-term preservation of nutritional status in this cohort. Mean (95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and -7.8 (-44.3, 28.8) kg/m2 × g/L at 5.5 years, respectively. No new safety issues or side effects were identified. These data represent the longest prospective evaluation of tafamidis to date, confirm a favorable safety profile, and underscore the long-term benefits of early intervention with tafamidis.

Trial registration: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and NCT00925002.

Keywords: ATTRV30M; Amyloidosis; TTR Val30Met; disease modification; transthyretin amyloidosis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amyloid Neuropathies, Familial / diagnosis
  • Amyloid Neuropathies, Familial / drug therapy*
  • Amyloid Neuropathies, Familial / physiopathology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Benzoxazoles / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Secondary Prevention


  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoxazoles
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT00409175
  • ClinicalTrials.gov/NCT00791492
  • ClinicalTrials.gov/NCT00925002