Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis

<p><strong>Declarations</strong></p> <p><strong>Funding</strong> The preparation of this review was not supported by any external funding.</p> <p><strong>Authorship and Conflict of interest</strong> Tina Nie, Young-A Heo and Matt Shirley are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to this article and are responsible for its content.</p> <p><strong>Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability </strong>Not applicable.</p> <p>Additional information about this Adis Drug Review can be found <a href="http://www.springer.com/gp/adis/products-services/adis-journals-newsletters/adis-drug-reviews" target="_blank"><strong>here</strong></a>.</p> <p><strong>Abstract </strong> </p> <p>Silencing the transthyretin (<em>TTR</em>) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra^®), an RNA interference (RNAi) therapeutic targeting <em>TTR</em> mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. <em>N</em>-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage. </p> <p>© Springer Nature Switzerland AG 2023</p>