Vutrisiran

Vutrisiran is a double-stranded small interfering ribonucleic acid (siRNA) that targets wild-type and mutant transthyretin (TTR) messenger RNA (mRNA). This siRNA therapeutic is indicated for the treatment of neuropathies associated with hereditary transthyretin-mediated amyloidosis (ATTR), a condition caused by mutations in the TTR gene. More than 130 TTR mutations have been identified so far, but the most common one is the replacement of valine with methionine at position 30 (Val30Met). The Val30Met variant is the most prevalent among hereditary ATTR patients with polyneuropathy, especially in Portugal, France, Sweden, and Japan. TTR mutations lead to the formation of misfolded TTR proteins, which form amyloid fibrils that deposit in different types of tissues. By targeting TTR mRNA, vutrisiran reduces the serum levels of TTR. Vutrisiran is commercially available as a conjugate of N-acetylgalactosamine (GalNAc), a residue that enables the delivery of siRNA to hepatocytes. This delivery platform gives vutrisiran high potency and metabolic stability, and allows for subcutaneous injections to take place once every three months. Another siRNA indicated for the treatment of polyneuropathy associated with hereditary ATTR is patisiran. Vutrisiran was approved by the FDA in June 2022.

Vutrisiran is a double-stranded small interfering ribonucleic acid (siRNA) that targets wild-type and mutant transthyretin (TTR) messenger RNA (mRNA). This siRNA therapeutic is indicated for the treatment of neuropathies associated with hereditary transthyretin-mediated amyloidosis (ATTR), a condition caused by mutations in the TTR gene. More than 130 TTR mutations have been identified so far, but the most common one is the replacement of valine with methionine at position 30 (Val30Met). The Val30Met variant is the most prevalent among hereditary ATTR patients with polyneuropathy, especially in Portugal, France, Sweden, and Japan. TTR mutations lead to the formation of misfolded TTR proteins, which form amyloid fibrils that deposit in different types of tissues. By targeting TTR mRNA, vutrisiran reduces the serum levels of TTR. Vutrisiran is commercially available as a conjugate of N-acetylgalactosamine (GalNAc), a residue that enables the delivery of siRNA to hepatocytes. This delivery platform gives vutrisiran high potency and metabolic stability, and allows for subcutaneous injections to take place once every three months. Another siRNA indicated for the treatment of polyneuropathy associated with hereditary ATTR is patisiran. Vutrisiran was approved by the FDA in June 2022.

Vutrisiran is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

• Polyneuropathies