Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial

Abstract

Background: Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score–Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial.

Methods: Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life–Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques.

Results: Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect.

Conclusions: These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP.

Trial registration number: NCT00409175.

Keywords:

• Amyloidosis
• disease-modifying drug
• familial amyloid neuropathy
• polyneuropathy
• tafamidis
• transthyretin

Acknowledgements

The authors thank the study investigators (Supplementary Appendix 1), personnel and patients for their important contributions. Medical writing support was provided by Sharmila Blows, PhD, and Susanne Vidot, PhD, of Engage Scientific Solutions and was funded by Pfizer.

Disclosure statement

D.K., J.S., M.S. and L.A. are employees of Pfizer. B.G. is an employee of inVentiv Health (Burlington, MA, USA), who provided statistical support, which was funded by Pfizer.

Additional information

Funding

This study was sponsored by Pfizer, New York, NY, USA. Medical writing support and statistical support was funded by Pfizer.