Mark S. Taylor (Australia)
Westmead Hospital and Westmead Clinical School, University of Sydney Department of Clinical Immunology and AllergyAuthor Of 1 Presentation
HELIOS-A: 9-MONTH RESULTS FROM THE PHASE 3 STUDY OF VUTRISIRAN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS WITH POLYNEUROPATHY
- Laura P. Obici (Italy)
Abstract
Background and Aims:
Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a progressive disease caused by misfolded transthyretin (TTR) that accumulates as amyloid fibrils in multiple tissues and organs. Vutrisiran, an investigational RNAi therapeutic for the treatment of ATTR amyloidosis, targets variant and wild-type TTR.
Methods:
HELIOS-A (NCT03759379) is a Phase 3, global, open-label study of vutrisiran 25 mg SC every 3 months in patients with ATTRv amyloidosis with polyneuropathy,randomized (3:1) to vutrisiran or patisiran, a reference comparator RNAi therapeutic approved for hATTR amyloidosis with polyneuropathy. Randomization was stratified by TTR genotype (V30M vs. non-V30M) and baseline NIS score (<50 vs ≥50). The APOLLO placebo arm (N=77) serves as external control for the primary and most secondary endpoints. Month 9 efficacy analyses include change from baseline in mNIS+7 (primary endpoint), Norfolk QOL-DN (secondary), and 10-meter walk test (10-MWT) (secondary), compared to APOLLO placebo arm.
Results:
HELIOS-A enrolled 164 patients (122 [74.4%] vutrisiran, 42 [25.6%] patisiran). Vutrisiran met the primary endpoint (p<0.001) and achieved statistical significance (p<0.001) for all planned secondary endpoints. The majority of patients showed improvement in neurologic impairment and quality of life relative to baseline. Vutrisiran demonstrated an acceptable safety profile; most common adverse events in vutrisiran-treated patients occurred at similar or lower rate versus the APOLLO placebo arm.
Conclusions:
The 9-month primary analysis demonstrates that vutrisiran improves neuropathy and QOL in patients with ATTRv amyloidosis with polyneuropathy. HELIOS-A will continue to investigate the efficacy and safety of vutrisiran through the 18-month treatment and extension periods.