vutrisiran + tafamidis

Amvuttra + Vyndaqel is a combination regimen consisting of vutrisiran (Amvuttra), a transthyretin (TTR)-directed small interfering RNA (siRNA), and tafamidis meglumine (Vyndaqel), an oral TTR stabilizer. Vutrisiran works by silencing TTR mRNA in hepatocytes, thereby reducing the production of both wild-type and variant TTR protein. Tafamidis binds to the thyroxine-binding sites of TTR, stabilizing the tetramer and preventing its dissociation into amyloidogenic monomers. This combination approach, which combines TTR silencing with TTR stabilization, has been evaluated in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) in the Phase 3 HELIOS-B trial, where patients on background tafamidis therapy were randomized to receive vutrisiran or placebo.