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HELIOS-A: Vutrisiran meets exploratory endpoints

Presented By
Dr Pablo García-Pavía, Hospital Universitario Puerta de Hierro Majadahonda, Spain
HFA 2022
Phase 3, HELIOS-A
The 18-months results of the HELIOS-A study showed that vutrisiran treatment improved NT-proBNP levels, with a trend towards improvement in echocardiographic parameters, compared with placebo. These benefits were observed in the general population and the prespecified cardiac subpopulation of the trial. Additionally, results from scintigraphy suggested potential regression of cardiac amyloid.

“Hereditary transthyretin amyloidosis (hATTR) is a rare, debilitating, and fatal disease,” introduced Dr Pablo García-Pavía (Hospital Universitario Puerta de Hierro Majadahonda, Spain) [1]. Vutrisiran is an investigational, subcutaneously administered small interfering RNA interface therapy for treating ATTR amyloidosis [2]. In the phase 3 HELIOS-A trial (NCT03759379), vutrisiran was compared with patisiran, an RNA interface therapy, administered via intravenous infusion and approved for treating polyneuropathy based on the results of the APOLLO trial (NCT01960348) [3]. The phase 3 HELIOS-A trial randomised 164 patients with hATTR amyloidosis 3:1 to vutrisiran or patisiran during the treatment period. After this period, all patients switched to receive vutrisiran and were compared with the placebo arm of the APOLLO trial. The current analysis of this trial discussed exploratory endpoints at 18 months in the general subpopulation and in a prespecified cardiac subpopulation.

Vutrisiran treatment improved NT-proBNP levels both the general population of vutrisiran receivers (adjusted geometric fold change ratio (0.480; P<0.0001) and in the cardiac subpopulation of vutrisiran receivers compared with the placebo group of the APOLLO trial (0.491; P=0.0004). Also, a trend towards improved echocardiographic parameters ‘cardiac output’ and ‘left ventricle end-diastolic volume’ was observed in the general population and in the cardiac subpopulation, as compared with placebo. Furthermore, scintigraphy imaging revealed that ‘99mTechnetium-normalised left ventricular total uptake’ was improved in 68% of the patients on vutrisiran at 18 months in all patients with a Perugini grade ≥2. Finally, the safety analysis did not reveal novel issues arising from the use of vutrisiran and most adverse events were of mild or moderate severity, resulting in an acceptable safety profile of the agent, as previously reported for patisiran [4]. Currently, the HELIOS-B trial is running to investigate the efficacy and safety of vutrisiran in patients with ATTR amyloidosis and cardiomyopathy.

    1. García-Pavía P, et al. HELIOS-A: 18-Month Exploratory Cardiac Results from the Phase 3 Study of Vutrisiran in Patients with Hereditary Transthyretin-Mediated Amyloidosis. LBT 1, Heart Failure 2022, 21–24 May, Madrid, Spain.

    2. Habtemariam BA, et al. Clin Pharmacol Ther. 2021;109(2):37–382

    3. Adams D, et al. N Engl J Med 2018;379:11–21.

    4. Adams D, et al. Lancet Nerol 2021;20:49–59.

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