The ongoing global, randomized, open-label, phase 3, HELIOS-A study evaluating the efficacy and safety of vutrisiran in participants with hereditary transthyretin amyloidosis, including transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), has published its 9-month primary analysis data.

The investigation enrolled 164 participants at 57 sites across Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Cyprus, France, Germany, Greece, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Portugal, Spain, Sweden, Taiwan, United Kingdom, and United States.

According to the study design, the first arm of participants (vutrisiran group) is to receive 25 mg of subcutaneous vutrisiran once every 3 months for 18 months of the treatment period, followed by subcutaneous injections of vutrisiran every 3 or 6 months during the randomized treatment extension period.

The second arm (patisiran group) is to receive an intravenous infusion of 0.3 mg/kg of patisiran once every 3 weeks for 18 months of the treatment period, followed by subcutaneous injections of vutrisiran every 3 or 6 months during the randomized treatment extension period.

Read more about AATR-CM experimental therapies

This study will use the placebo arm of the APOLLO study as an external comparator for the primary and most other efficacy endpoints during the treatment period of 18 months.

The researchers analyzed the change from baseline in the Modified Neurologic Impairment Score +7 at 9 months between the vutrisiran group and the APOLLO group as the primary outcome measure, but no statistically significant difference was found.

There were no notable differences between the vutrisiran group and the APOLLO group regarding the change from baseline in the Norfolk Quality of Life-Diabetic Neuropathy total score at month 9 or in the change from baseline in the Timed 10-Meter Walk Test at month 9. No data was reported for other secondary outcome measures.

All-cause mortality was higher in the patisiran group (7.14%) compared with the vutrisiran group (1.64%). The rate of nonserious adverse events was 63.93% in the vutrisiran group and 73.81% in the patisiran group.

Read more about ATTR-CM treatment

The rate of serious adverse events was notably higher in the patisiran group (40.48%) compared with the vutrisiran group (17.21%). The patients most often experienced congestive heart failure, infusion-related immune reactions, infusion site cellulitis, COVID-19, pneumonia, falls, and foot fractures.

The study was started later than expected, in February 2019, and will probably be completed by October 2026 instead of May 2024. The sponsor is Alnylam Pharmaceuticals.

Reference

A study of vutrisiran (ALN-TTRSC02) in patients with hereditary transthyretin amyloidosis (hATTR Amyloidosis). ClinicalTrials.gov. Published online November 30, 2018. Last updated August 21, 2023. Accessed August 27, 2023.