FDA Places Vutrisiran on Fast Track as Potential FAP Treatment for Adults

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by Joana Carvalho |

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The U.S. Food and Drug Administration (FDA) has granted fast track designation to Alnylam Pharmaceuticalsvutrisiran as a potential treatment of adults with familial amyloid polyneuropathy (FAP).

Fast track is intended to accelerate the development and review of investigational therapies aimed at treating serious or life-threatening conditions, and addressing an unmet medical need. With this designation, Alnylam is eligible to submit a rolling new drug application for possible regulatory approval of vutrisiran.

Vutrisiran, formerly known as ALN-TTRsc02, is an RNA-targeted therapy designed to stop the production of misfolded transthyretin — the abnormal protein clumping in amyloid deposits that cause FAP, also known as hereditary transthyretin amyloidosis.

The therapy does so by targeting and silencing transthyretin’s messenger RNA (produced from DNA), thereby preventing cells from using the mutated RNA molecule as a template to produce a misfolded transthyretin protein.

A Phase 1 trial in healthy volunteers (NCT02797847) showed that vutrisiran was well-tolerated and lowered transthyretin levels in the blood.

“Vutrisiran has demonstrated an encouraging safety profile in the Phase 1 study, with infrequent quarterly dosing … which potentially reduces the burden of care for this progressive, life-threatening and multisystem disease. We are therefore pleased that the FDA has granted vutrisiran Fast Track designation,” Rena Denoncourt, leader of vutrisiran’s clinical program at Alnylam, said in a press release.

The safety and efficacy of vutrisiran are currently being investigated in two Phase 3 trials — HELIOS-A (NCT03759379) and HELIOS-B (NCT04153149) — in adults with FAP. Both studies are part of vutrisiran’s development program that aims to provide solid evidence of the therapy’s effectiveness in people with distinct manifestations of FAP.

In these two studies, participants are receiving under-the-skin injections of vutrisiran at a dose of 25 mg, every 12 weeks (three months).

In HELIOS-A, patients given intravenous infusions (directly into the bloodstream) of Onpattro (patisiran) — the first RNA-targeted therapy approved in the U.S. to treat FAP — at 0.3 mg/kg every three weeks serve as a control group. In HELIOS-B, some are being randomized to a placebo at the same dosing schedule of vutrisiran.

In March, the company announced it had completed enrollment for HELIOS-A, which now has 160 patients from 22 countries worldwide. Enrollment for HELIOS-B, which will assess the efficacy and safety of vutrisiran in up to 600 adults with FAP and heart disease (cardiomyopathy), is still ongoing in the U.S. and Latvia.

Top-line data from HELIOS-A is expected in early 2021, and from HELIOS-B in mid-2024.

Vutrisiran was given orphan drug status for the treatment of FAP in both the U.S. and the E.U. in 2018.