Vyndaqel(tafamidis)

Vyndaqel (tafamidis) is indicated for the treatment of transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment. Tafamidis binds to transthyretin (TTR) with binding constants (KD1) of 2 nM and 3 nM (by ITC), and (KD2) of 154 nM and 278 nM (by ITC). It inhibits fibril formation with an EC50 of 2.7-3.2 µM, with a tafamidis:TTR stoichiometry range of 0.75-0.9 at EC50. Tafamidis has an affinity for albumin (KD) of 2,500 nM.

In clinical trials, 45.3% of patients were NIS-LL responders (ITT population), with a p-value of 0.0367 for sensitivity analysis. The trial was a Phase II/III study with an 18-month treatment duration, involving participants aged 18-75 years old. The adjusted sample size per arm was 61-64 patients. Tafamidis has high plasma protein binding (>99%). The mean human steady-state Cmax of tafamidis is 7.4 mM (2.28 µg/ml).

Regulatory milestones include an Orphan medicinal product designation on 28 August 2006, and a Marketing Authorisation application submission on 28 July 2010. A CHMP positive opinion was issued on 21 July 2011, and a positive opinion for marketing authorisation was given on 12 December 2019. The orphan medicinal product prevalence is less than 0.1 per 10,000 EU population.