Long-Term Use Of Tafamidis In Transthyretin Familial Amyloid Polyneuropathy: A Single Center Experience

OBJECTIVE: To describe our experience with tafamidis in transthyretin familial amyloid polyneuropathy (TTR-FAP) patients at Hospital de Santo Antonio in Porto, Portugal, who have been treated with tafamidis for up to five years. BACKGROUND: TTR-FAP is a progressive neurodegenerative and invariably fatal disorder for which liver transplant has been the only accepted treatment. Tafamidis is a small molecule that prevents TTR amyloid formation and has been shown to delay neurologic impairment in a pivotal clinical trial. DESIGN/METHODS: Patients were initially enrolled in an 18-month, double-blind, randomized, placebo-controlled trial (Study Fx-005). Completers from either treatment arm received tafamidis in a 12-month, open-label extension of the trial (Study Fx-006) and were permitted to continue tafamidis treatment in an ongoing, open-label trial (Study Fx1A-303) to evaluate the long-term effects of tafamidis. RESULTS: As of September 2012, 22 and 21 patients had completed 3.5 and 5 years of tafamidis treatment, respectively. At the beginning of Fx-005 (Month 0), all were considered to have some degree of peripheral and/or autonomic neuropathy with some perceived functional disability (Karnofsky performance status score ≥50) but without assistance required for ambulation (Stage 1 of disease). Our observation of these patients indicates that at Month 54, all have remained in Stage 1 without major progression of neurologic impairment related to mobility. Interestingly, a delayed-start effect was evident: patients initiated on tafamidis in Fx-005 experienced less decline from baseline in Neuropathy Impairment Score–Lower Limbs (NIS-LL) than patients initiated on placebo (least squares means ±standard error: tafamidis-tafamidis 2.00±2.29, n=19; placebo-tafamidis 10.16±2.27, n=17; P =0.01). At Month 42, change from baseline in NIS-LL muscle weakness subscores also had declined to a lesser extent in tafamidis-tafamidis patients (0.87±1.69, n=22 vs. 5.40±1.65, n=23; P= 0.06). CONCLUSIONS: Long-term use of tafamidis for the treatment of TTR-FAP results in a significant reduction in disease progression. Supported by: FoldRx Pharmaceuticals, which was acquired by Pfizer Inc in October 2010. Disclosure: Dr. Coelho9s institution has received research support from Pfizer Inc and Alnylam. Dr. Silva has received personal compensation from Biogen Idec, Sanofi, and Novartis for consulting services and serving on a scientific advisory board. Dr. Maia has nothing to disclose. Dr. Mandel has received personal compensation for activities with Pfizer as an employee. Dr. Rosas has received personal compensation for activities with Pfizer Inc. as an employee. Dr. Karayal has received personal compensation for activities with Pfizer Inc. as an employee. Dr. Karayal holds stock and/or stock options in Pfizer, which sponsored research in which Dr. Karayal was involved in an investigator.