FDA Approves Vutrisiran for Polyneuropathy of hATTR Amyloidosis

The Food and Drug Administration approved vutrisiran (Amvuttra; Alnylam Pharmaceuticals, Cambridge, MA) for adults with polyneuropathy in hereditary transthyretin-mediated (hATTR) amyloidosis treatments. Vutrisiran is an interfering RNA (RNAi) therapy administered subcutaneously every 3 months. 

“The FDA approval of AMVUTTRA is very encouraging for the hATTR amyloidosis community, who need additional therapies to address the polyneuropathy of this progressive, life-threatening, multisystem disease,” said Michael Polydefkis, MD, MHS, professor, Johns Hopkins Neurology and HELIOS-A Study Investigator. “AMVUTTRA is a new therapeutic option that has demonstrated the potential to halt or reverse polyneuropathy progression in patients with an acceptable safety profile, along with an infrequent, subcutaneous dosing regimen that may also help to improve the disease management experience for patients.”

In the HELIOS-A (NCT03759379) phase 3 study, participants treated with vutrisiran had a mean 2.2-point improvement on the modified Neuropathy Impairment Score +7 (mNIS+7). In contrast, participants in the APOLLO (NCT01960348) phase 3 study of patisiran had a 14.8-point mean worsening, for 17.0-point mean difference (P<.0001). After 9 months of treatment, 50% of those treated with vutrisiran had improved neuropathy.  Participants treated with vutrisiran vs placebo also had significant improvements on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) score and timed 10-meter walk test (10-MWT). 

In the 9 months of the study, there were no treatment-related discontinuations or deaths. The most common adverse event with vutrisiran were arthralgia (11%), dyspnea (7%) and vitamin A decreased (7%). There were 5 participants who reported to have mild and transient injection site reactions.

“Today we celebrate the FDA’s approval of vutrisiran, a welcomed treatment option for hATTR amyloidosis patients experiencing the challenges of the polyneuropathy of the disease,” said Isabelle Lousada, Founder and CEO, Amyloidosis Research Consortium. “With this approval, Alnylam has expanded treatment options that may support improvements in quality of life, providing hope for patients and families in the amyloidosis community.”