FDA Approves Amvuttra for Neuropathy Associated with Rare Disease

The FDA has approved Alnylam Pharmaceuticals’ Amvuttra (vutrisiran), an RNAi therapeutic administered via subcutaneous injection once every three months for the treatment of the polyneuropathy associated with hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

hATTR amyloidosis is a rare, inherited, rapidly progressive, and fatal disease caused by mutations of the transthyretin (TTR) gene. In hATTR, amyloid proteins build up the heart, kidneys, liver and other organs. Generally, patients first present with neuropathy, damage to nerves that results in numbness and muscle weakness. In addition to polyneuropathy, hATTR amyloidosis can lead the loss of the ability to walk unaided, a reduced quality of life, and a decline in cardiac functioning.

Michael Polydefkis, M.D.

“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,” Michael Polydefkis, M.D., professor, Johns Hopkins Neurology and HELIOS-A study investigator, said in a press release

The FDA approval is based on positive nine-month results from the HELIOS-A phase 3 study, that showed Amvuttra improved the signs and symptoms of polyneuropathy, with more than 50% of patients experiencing halting or reversal of their disease. In the trial, 164 patients with hATTR amyloidosis were randomized to receive either Amvuttra via subcutaneous injection once every three months or Onpattro (patisiran) via intravenous infusion once every three weeks (reference group) for 18 months, or placebo.

Onpattro is another product developed by Alnylam that was approved by the FDA in August 2018 also to treat polyneuropathy associated with hATTR.

Amvuttra met the primary endpoint, a change from baseline in neuropathy score, resulting in a 2.2 mean improvement compared with a 14.8 mean worsening in the score in patients in the placebo group. Additionally, 50% of patients treated with Amvuttra experienced improvement the neuropathy. Amvuttra also met all secondary endpoints, with improvement in quality of life and the 10-minute walk test.

The most commonly reported adverse events patients included joint stiffness (11%), labored breathing (7%) and a decrease in vitamin A (7%). Injection site reactions were reported in 5 patients (4%) and were all mild and transient. There were no drug-related discontinuations or deaths.

RNAi (RNA interference) is a natural cellular process of gene silencing that was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. Small interfering RNA (siRNA), the molecules that mediate RNAi, comprise Alnylam’s RNAi therapeutic platform.