Vutrisiran Wins Fast Track Designation for Polyneuropathy in hATTR Amyloidosis


Alnylam Pharmaceuticals recently completed enrollment in the phase 3 HELIOS-A clinical trial of the drug.

Rena Denoncourt

Rena Denoncourt

Alnylam Pharmaceuticals has announced that the FDA has granted its drug vutrisiran fast track designation for the treatment of polyneuropathy associated with hereditary transthyretin-mediated (hATTR) amyloidosis in adults.1

The investigational agent, which is delivered via subcutaneous injection, is destined to be part of a 1-2 punch alongside Alnylam’s currently approved therapy patisiran (Onpattro), which is approved for the same indication but delivered via intravenous infusion.

“Vutrisiran has demonstrated an encouraging safety profile in the phase 1 study, with infrequent quarterly dosing with low-volume, subcutaneous administration which potentially reduces the burden of care for this progressive, life-threatening and multisystem disease,” said Rena Denoncourt, Vutrisiran Program Leader at Alnylam, in a statement.1

The RNAi therapy, which has also been granted orphan drug designation, is designed to target messenger RNA and effectively block the production of wild-type and mutant transthyretin, as well as help facilitate the clearance of TTR amyloid deposits in tissue.

Earlier this year, enrollment in the HELIOS-A phase 3, randomized, open-label clinical trial (NCT03759379) of vutrisiran was completed, with 160 patients taking part across 68 trial sites in 22 countries.2 The trial will evaluate the safety and efficacy of vutrisiran against its sister drug patisiran. Patients will be randomized 3:1 to receive either 25 mg subcutaneous vutrisiran once every 12 weeks or 0.3 mg intravenous patisiran once every 3 weeks. The co-primary end points of the trial are change from baseline in modified Neurologic Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) score at 9 months. Notably, most end points will compare results in the vutrisiran arm to the placebo arm of the phase 3 APOLLO study, which evaluated patisiran in people with hATTR amyloidosis with polyneuropathy.

Additional end points in the HELIOS-A trial include change from baseline in timed 10-meter walk test (10-MWT), modified body mass index (mBMI), and Rasch-built Overall Disability Scale (R-ODS). The percent reduction in serum TTR levels in the vutrisiran arm will be compared to the within-study patisiran arm. In addition, investigators will determine the effect of vutrisiran on other aspects of the disease, including cardiac amyloid involvement.

Vutrisiran is also being evaluated against placebo in the ongoing HELIOS-B phase 3 clinical trial (NCT04153149) in patients with ATTR amyloidosis with cardiomyopathy. The composite primary outcome of that trial, which has a target enrollment of 600 participants, is all-cause mortality and recurrent cardiovascular hospitalizations at 30 months.

Alnylam plans to readout topline results from HELIOS-A sometime early next year.


1. Alnylam Receives Fast Track Designation for Vutrisiran for the Treatment of the Polyneuropathy of hATTR Amyloidosis [news release]. Cambridge, MA: Alnylam Pharmaceuticals. April 14, 2020. Accessed April 21, 2020.

2. Alnylam Completes Enrollment of HELIOS-A Phase 3 Study of Vutrisiran for the Treatment of hATTR Amyloidosis with Polyneuropathy [news release]. Cambridge, MA: Alnylam Pharmaceuticals. February 18, 2020. Accessed April 21, 2020.

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