Abstract Details

Title HELIOS-A: 9-month Results from the Phase 3 Study of Vutrisiran in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy

Topic General Neurology

Presentation(s) S13 - Advances in General Neurology (2:00 PM-2:08 PM)

Poster/Presentation
Number 001

Objective

Present 9-month efficacy and safety from the HELIOS-A Phase 3 study of vutrisiran, an investigational RNA interference (RNAi) therapeutic.

Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is an underdiagnosed, rapidly progressive, and fatal disease caused by misfolded transthyretin (TTR) that accumulates as amyloid fibrils in multiple tissues and organs. Vutrisiran is an RNAi therapeutic in development for the treatment of ATTR amyloidosis by targeting liver-expressed variant and wild type TTR. Vutrisiran utilizes the Enhanced Stabilization Chemistry (ESC)-GalNAc platform designed to provide increased potency and high metabolic stability. In a Phase 1 study of healthy volunteers, a single dose of vutrisiran 25 mg subcutaneously (SC) resulted in 80% mean maximum reduction in serum TTR maintained for 90 days.

Design/Methods HELIOS-A is a Phase 3, global, open-label study of vutrisiran 25 mg SC once every 3 months in patients with ATTRv amyloidosis with polyneuropathy (NCT03759379). Patients were randomized (3:1) to vutrisiran or patisiran, a reference comparator RNAi therapeutic approved for hATTR amyloidosis with polyneuropathy based on the APOLLO study. Randomization was stratified by TTR genotype (V30M vs. non-V30M) and baseline NIS score (<50 vs ≥50). The APOLLO placebo group (N=77) serves as an 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 (secondary), compared to APOLLO placebo group.

Results HELIOS-A enrolled 164 patients (122 [74.4%] vutrisiran, 42 [25.6%] patisiran) across 57 sites in 22 countries. Baseline demographics, the 9-month primary endpoint, secondary endpoints, and safety results will be presented.

Conclusions Vutrisiran has the potential to address a significant unmet need for patients with ATTRv amyloidosis with polyneuropathy by offering an additional treatment option. HELIOS-A will continue to investigate the efficacy and safety of vutrisiran through an 18-month treatment period and 18-month extension period.

Authors/Disclosures
David D. Adams (APHP) PRESENTER	David D. Adams has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ALNYLAM. David D. Adams has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer.
	No disclosure on file
	No disclosure on file
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital)	Dr. Coelho has nothing to disclose.
Violaine Plante-Bordeneuve, MD (CHU Henri Mondor)	Dr. Plante-Bordeneuve has nothing to disclose.
John L. Berk	John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca/IONIS. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eidos/BridgBio. John L. Berk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia Therapeutics. John L. Berk has received research support from Alnylam . John L. Berk has received research support from Ionis. John L. Berk has received research support from Eidos/Bridgbio.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Yoshiki Sekijima, MD, PhD	Yoshiki Sekijima, "MD, PhD" has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam. Yoshiki Sekijima, "MD, PhD" has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Pfizer.
Laura Piera Obici (Fondazione IRCCS Policlinico San Matteo)	No disclosure on file
	No disclosure on file
Seth Arum (Alnylam Pharmaceuticals)	Seth Arum has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. Seth Arum has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer.
Rebecca Shilling (Alnylam Pharmaceuticals)	Rebecca Shilling has received personal compensation for serving as an employee of argenx pharmaceuticals. Rebecca Shilling has stock in argenx pharmaceuticals. Rebecca Shilling has received intellectual property interests from a discovery or technology relating to health care.
John Vest	John Vest has received personal compensation for serving as an employee of Alnylam Pharmaceuticals. John Vest has received stock or an ownership interest from Alnylam Pharmaceuticals. John Vest has received intellectual property interests from a discovery or technology relating to health care.
Michael J. Polydefkis, MD, FAAN (Johns Hopkins University School of Medicine)	Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceutical . Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer.

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