The Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for vutrisiran for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults.
HATTR polyneuropathy is caused by the accumulation of abnormal amyloid protein in peripheral nerves, the heart, and other organs. Vutrisiran is an investigational subcutaneously administered RNAi therapeutic that is designed to block the production of wild-type and mutated transthyretin protein.
The NDA application is supported by data from the global, randomized, open-label phase 3 study HELIOS-A (ClinicalTrials.gov Identifier: NCT03759379), which evaluated the efficacy and safety of vutrisiran in 164 adults with hATTR amyloidosis. Patients were randomized 3: 1 to receive vutrisiran (n = 122) 25 mg subcutaneously once every 3 months or patisiran (n = 42) 0.3 mg / kg intravenously once every 3 weeks for 18 months. In the study, the placebo arm of the phase 3 study APOLLO (ClinicalTrials.gov Identifier: NCT01960348) was used as the external comparator for the primary and most of the secondary endpoints.
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The primary endpoint was the change in the modified neuropathy impairment score (mNIS + 7) compared to the baseline value after 9 months. Key secondary endpoints included changes in quality of life as assessed using the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and gait speed as assessed using the 10-meter timed walk test (10-MWT) .
The results showed that vutrisiran met the primary endpoint, achieving a mean decrease in the mNIS + 7 score of 2.24 points after 9 months, compared to a mean increase of 14.76 points for the external placebo arm (mean difference 17 , 0 points; P = 3.54 × 10-12). These findings in the Vutrisiran arm were consistent with those in the Patisiran arm.
Treatment with vutrisiran resulted in a mean decrease in the Norfolk QoL DN score of 3.3 points after 9 months compared to a mean increase of 12.9 points in the external placebo arm (mean difference 16.2 points; P. = 5.43 x 10-9). The patients treated with vutrisiran remained stable in walking speed, while the walking speed of the patients in the external placebo arm deteriorated (P = 3.10 × 10–5).
Vutrisiran was associated with an 83% reduction in mean serum transthyretin levels at steady state. Improvements in other exploratory endpoints were also observed, including the cardiac endpoint of NT-proBNP, change in modified body mass index, and the Rasch-built total disability scale.
In terms of safety, treatment-related side effects included diarrhea, extremity pain, falls, and urinary tract infections. Dyslipidemia and urinary tract infections have been reported as serious drug-related adverse reactions associated with vutrisiran.
The target date of the Act on Charges for Prescription Drugs (PDUFA) has been set for the application to be April 14, 2022. “Once approved quarterly, subcutaneous vutrisiran can represent a new treatment option that potentially reverses the manifestations of polyneuropathy,” said Rena Denoncourt, vice president, TTR Franchise Lead.
The FDA previously granted Vutrisiran orphan drug and fast track status for the treatment of the polyneuropathy of hATTR amyloidosis in adults.
References
- Alnylam announces that the US Food and Drug Administration has approved a new drug for the investigational drug vutrisiran for the treatment of the polyneuropathy of hereditary ATTR amyloidosis. [press release]. Cambridge, MA: Alnylam Pharmaceuticals, Inc .; 06/24/2021.
- Alnylam presents positive results from the HELIOS A phase 3 study with the investigational product Vutrisiran. [press release]. Cambridge, MA: Alnylam Pharmaceuticals, Inc .; April 19, 2021.
This article originally appeared on MPR
