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At 9 months, vutrisiran was found to improve multiple disease-relevant endpoints of hereditary transthyretin-mediated (hATTR) amyloidosis, according to study results presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, held from April 2 to April 7 in Seattle, Washington, and virtually from April 24-26, 2022.
hATTR amyloidosis is a progressive, life-threatening disease which can cause polyneuropathy. The drug vutrisiran is an ribonucleic acid (RNA) interference (RNAi) therapeutic which targets the wild-type and mutational variants of the gene transthyretin (TTR) which is affected in hATTR amyloidosis. The objective of the current study was to evaluate the safety and efficacy of vutrisiran using data from an ongoing trial.
The HELIOS-A trial is an ongoing, 18-month, phase 3 study. Patients with hATTR amyloidosis with polyneuropathy were randomized in a 3:1 ratio to receive 25 mg subcutaneous vutrisiran (n=122) every three months or 0.3 mg/kg intravenous patisiran (n=42) every three weeks. Patisiran is an RNAi therapeutic which was established as a reference comparator in the APOLLO study. The placebo cohort from the APOLLO study (n=77) was used as an external control for this study. The primary endpoint was change in neuropathy impairment as measured by the modified Neuropathy Impairment Score +7 (mNIS+7) at month 9.
The vutrisiran, patisiran, and external placebo cohorts were well balanced at baseline.
At nine months, patients who received vutrisiran exhibited sustained reduction of serum TTR levels.
The change in mNIS+7 from baseline was -2.2±1.4 among vutrisiran recipients and -14.8±2.0 for placebo recipients (mean difference, -17.0; P =3.5´10-12). In addition, N-terminal pro-brain natriuretic peptide levels were improved in the vutrisiran group (adjusted geometric fold change ratio, 0.6; P =9.2´10-7).
Vutrisiran was observed to significantly improve Norfolk Quality of Life-Diabetic Neuropathy score, gait speed during the ten-meter walk test, modified body mass index nutritional status, and Rasch-build Overall Disability Scale score, compared with placebo.
Most of the observed adverse events among the vutrisiran cohort were mild or moderate. No patient discontinued vutrisiran use and no deaths occurred.
This study was limited by using an external control cohort.
“At 9 months, vutrisiran significantly improved multiple disease-relevant endpoints vs. external placebo, with an acceptable safety profile, indicating benefit across numerous important disease manifestations,” the researchers concluded.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Adams D, Tournev I, Taylor M, et al. HELIOS-A: Results from the Phase 3 Study of Vutrisiran in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy. Presented at: the 2022 AAN Annual Meeting; April 2-7, 2022; Seattle, Washington; April 24-26, 2022; virtual meeting Abstract S8.003.