The U.S. Food and Drug Administration (FDA) has approved of vutrisiran (Amvuttra) for the treatment of polyneuropathy observed in patients with hereditary ATTR (hATTR) amyloidosis.

hATTR amyloidosis is an inherited and progressively debilitating disease caused by mutations of the TTRgene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. These mutations cause abnormal amyloid proteins to accumulate and damage organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations.

Vutrisiran is an RNAi therapeutic administered subcutaneously quarterly. It is a double‑stranded small interfering RNA (siRNA) that targets mutant and wild‑type TTR mRNA.

The approval of vutrisiran was largely based on positive 9-month results from the HELIOS-A phase 3 study, which evaluated the safety and efficacy of vutrisiran compared to patisiran. The 9-month results achieved the study’s primary endpoint, the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months. Treatment with vutrisiran (N=114) resulted in a 2.2 point mean decrease (improvement) in mNIS+7 from baseline as compared to a 14.8 point mean increase (worsening) reported for the external placebo group from the phase APOLLO study of patisiran (N=67), resulting in a 17.0 point mean difference relative to placebo (P<0.0001). By 9 months, 50% of patients treated with vutrisiran experienced improvement in neuropathy impairment relative to baseline. Vutrisiran also met all secondary endpoints, demonstrating improvement in quality of life and improvement in gait speed, both compared to the external placebo group. The majority of patients experienced improvement in neuropathy and in quality of life relative to baseline, demonstrating the potential for vutrisiran to reverse polyneuropathy manifestations of hATTR amyloidosis. 18-month results were consistent with 9-month data, with vutrisiran achieving statistically significant improvements compared to external placebo for all secondary endpoints.

Additionally, vutrisiran demonstrated an encouraging safety profile with no drug-related discontinuations or deaths. The most common adverse events in vutrisiran-treated patients included arthralgia (11%), dyspnea (7%) and vitamin A decrease (7%). Injection site reactions were reported in 5 patients (4%), all of which were mild and transient.

To learn more about hATTR amyloidosis and other rare neurological conditions, visit