FDA to Decide on Vutrisiran’s Possible Approval by April 2022

Alnylam Pharmaceuticals’ application for the approval of vutrisiran, its investigational therapy for familial amyloid polyneuropathy (FAP), is being reviewed by the U.S. Food and Drug Administration (FDA), with a decision expected by April 14 of next year.

The agency has indicated that it is not currently planning to hold an advisory committee meeting as part of the review process.

“We are excited that the FDA has accepted our [application] for vutrisiran,” Rena Denoncourt, vice president, TTR franchise lead at Alnylam, said in a press release. “Today’s announcement marks another important milestone as we work to make vutrisiran available to [FAP patients].”

The company’s application is supported by data from the ongoing Phase 3 HELIOS-A trial (NCT03759379). The study, sponsored by Alnylam, enrolled 164 participants with FAP who were assigned to treatment with vutrisiran or Onpattro (patisiran).

Also developed by Alnylam, Onpattro is an approved treatment for FAP in the U.S. Both vutrisiran and Onpattro use a process called RNA interference to lower the production of TTR, the faulty protein that causes FAP. However, vutrisiran is designed to have greater stability, potentially allowing for a stronger and long-lasting effect compared with Onpattro.

In HELIOS-A, vutrisiran was administered by a subcutaneous (under-the-skin) injection every three months, and Onpattro was given intravenously (by an infusion directly into the bloodstream) every three weeks.

Nine-month data from the trial showed that, over nine months of treatment, most participants given vutrisiran experienced less severe neurologic impairments and reported improvements in their quality of life. Treated participants also had few changes in the time it took them to walk 10 meters (about 33 feet). In contrast, participants given a placebo in earlier trials of Onpattro experienced substantial worsening of neurologic impairment, quality of life, and walking ability over the same period of time.

Vutrisiran was generally safe and well-tolerated in HELIOS-A. Common adverse events associated with the medication included diarrhea, pain in the extremities, falls, and urinary tract infections. Two serious adverse events — a urinary tract infection and an instance of elevated levels of fatty molecules in the bloodstream (dyslipidemia) — were also reported.

“If approved, once-quarterly, subcutaneously administered vutrisiran may represent a new treatment option that potentially reverses polyneuropathy manifestations of disease,” Denoncourt said.

Alnylam is planning to submit similar approval requests for vutrisiran in Europe, Brazil, and Japan based on data from HELIOS-A.