Vutrisiran Approved for Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis

Amvuttra is a subcutaneously-administered RNAi therapeutic designed to block the production of wild-type and mutant transthyretin protein.

The Food and Drug Administration (FDA) has approved Amvuttra (vutrisiran) for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

Polyneuropathy of hATTR amyloidosis is caused by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs. Amvuttra contains vutrisiran, a chemically modified double-stranded small interfering ribonucleic acid that targets mutant and wild-type transthyretin (TTR) messenger RNA, resulting in a reduction of serum TTR protein and TTR protein deposits in tissues.

The approval was based on data from the global, randomized, open-label phase 3 HELIOS-A study ( Identifier: NCT03759379), which evaluated the efficacy and safety of Amvuttra in 164 adults with hATTR amyloidosis. Patients were randomly assigned 3:1 to receive Amvuttra 25 mg subcutaneously once every 3 months (n=122) or patisiran 0.3 mg/kg intravenously once every 3 weeks (n=42) for 18 months. The study used the placebo arm of the phase 3 APOLLO study ( Identifier: NCT01960348) as an external comparator for the primary and most secondary endpoints.

The primary endpoint was the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months. Key secondary endpoints included changes in quality of life, assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), and gait speed, assessed by the timed 10-meter walk test (10-MWT).

Results showed that Amvuttra met the primary endpoint demonstrating a 2.24 point mean decrease (improvement) in mNIS+7 score at 9 months compared with a 14.8 point mean increase (worsening) for placebo (mean difference, -17.0 points; 95% CI, -21.8, -12.2; P <.001). Findings in the Amvuttra arm were consistent with those observed in the patisiran arm. 

Additionally, Amvuttra met all secondary endpoints including a 3.3 point mean decrease (improvement) in Norfolk QoL-DN score at 9 months compared with a 12.9 point mean increase (worsening) for the external placebo arm (mean difference, -16.2 points; 95% CI, -21.7, -10.8; P <.001). Statistically significant improvements in the 10-meter walk test were also observed (mean difference, 0.13; 95% CI, 0.07-0.19; P <.001).

The most common adverse reactions reported were arthralgia, dyspnea, and decreased vitamin A. 

Amvuttra is supplied as a 25 mg/0.5 mL solution in a single-dose prefilled syringe. Treatment is administered by subcutaneous injection once every 3 months by a health care professional.

“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.”

Amvuttra is expected to be available in early July 2022.


  1. Alnylam announces FDA approval of Amvuttra (vutrisiran), an RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. News release. Alnylam Pharmaceuticals, Inc. Accessed June 13, 2022.
  2. Amvuttra. Package insert. Alnylam Pharmaceuticals, Inc.; 2022. Accessed June 14, 2022.

This article originally appeared on MPR