Tafamidis: A Review in Transthyretin Amyloidosis with Polyneuropathy.

Transthyretin amyloidosis with polyneuropathy (ATTR-PN), a rare and progressive hereditary disorder, results from mutations in the gene coding for the transthyretin (TTR) protein that destabilize the protein's tetrameric structure. In over 40 countries worldwide, tafamidis (Vyndaqel®) is approved for the treatment of TTR amyloidosis in adults with stage 1 symptomatic polyneuropathy, to delay peripheral neurological impairment. Tafamidis is administered orally once daily, as a soft capsule. Evidence from clinical studies, including an 18-month placebo-controlled trial and subsequent long-term, open-label extension studies (providing data from ≤ 6 years of treatment), indicate that tafamidis slowed deterioration of neurological function and maintained health-related quality of life in patients with early-stage ATTR-PN and the Val30Met mutation. TTR tetramers were stabilized in nearly all patients, and nutritional status was generally maintained or improved. Similar benefit was seen with tafamidis over 12 months in a noncomparative trial in patients with non-Val30Met ATTR-PN, although disease progression in this population (which was older and had had ATTR-PN for longer than Val30Met patients) became more notable with continued therapy in an extension study. Data for up to 10 years from large registry and referral centre studies support the long-term effectiveness and safety of tafamidis in delaying disease progression and conferring survival benefits in patients with stage 1 ATTR-PN. Tafamidis was generally well tolerated, with no new safety signals detected during the long-term trial or real-world experience. Thus, based on up to 10 years' experience, tafamidis continues to be a valuable option in the treatment of early-stage ATTR-PN.