Effects of tafamidis treatment on transthyretin (TTR) stabilization, efficacy, and safety in Japanese patients with familial amyloid polyneuropathy (TTR-FAP) with Val30Met and non-Val30Met: A phase III, open-label study

• The efficacy and safety of 20 mg tafamidis in patients with TTR-FAP was evaluated.
• All 10 patients achieved TTR stabilization (primary endpoint) at Weeks 8 and 26.
• Minimal neurological progression was observed as measured by NIS-LL.
• Nutrition status (mBMI) improved over the study while TQOL was variable.
• Tafamidis slows neurological progression and improves nutrition status in TTR-FAP.

IntroductionThe efficacy and safety of tafamidis in transthyretin (TTR) familial amyloid polyneuropathy (TTR-FAP) were evaluated in this open-label study.MethodsJapanese TTR-FAP patients (n = 10; mean age 60.1 years) received tafamidis meglumine (20 mg daily; median treatment duration 713.5 days). The primary endpoint was TTR stabilization at Week 8. Secondary endpoints included Neuropathy Impairment Score-Lower Limb (NIS-LL), Norfolk QOL-DN total quality of life (TQOL), and modified body mass index (mBMI).ResultsTTR stabilization was achieved in all patients at Weeks 8 and 26, 9 out of 10 patients at Week 52, and 8 out of 10 patients at Week 78. The percentage (95% CI) of NIS-LL responders (increase from baseline in NIS-LL < 2) was 80.0% (44.4, 97.5), 60.0% (26.2, 87.8), and 40.0% (12.2, 73.8) and mean(SD) NIS-LL change from baseline was 2.1 (5.6), 3.6 (4.4), and 3.3 (4.7), at Weeks 26, 52, and 78, respectively. Mean (SD) changes from baseline in TQOL and mBMI at Weeks 26, 52, and 78 were 11.8 (20.0), 9.1 (12.5), and 10.8 (13.7) for TQOL, and 26.6 (61.9), 64.9 (80.0), and 53.7 (81.4) for mBMI, respectively. Ambulation status was preserved in 4 out of 8 patients at Week 78. Most adverse events (AEs) were mild/moderate, with no discontinuations due to AEs.ConclusionsTafamidis stabilized TTR, was safe and well-tolerated, and was effective over 1.5 years in slowing neurologic progression and maintaining TQOL and nutrition status in TTR-FAP.