CAMBRIDGE, Mass. & TARRYTOWN, N.Y.– Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Regeneron Pharmaceuticals (Nasdaq: REGN) announced today preliminary Phase 1 data supporting the clinical advancement of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH).
After single-dose evaluation in healthy adult volunteers (Part A), multiple doses of ALN-HSD are being studied in adult patients with NASH (Part B). Patients in the first two Part B cohorts (200 and 400 mg quarterly) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. In the first two Part B cohorts, ALN-HSD was associated with robust target knockdown and numerically lower liver enzymes and biopsy-derived nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS)* over six months in patients receiving ALN-HSD (N=20) relative to placebo (N=4). The study was not powered to achieve statistical significance on these endpoints, and the primary outcome measure is frequency of adverse events. ALN-HSD has exhibited an encouraging safety and tolerability profile to date; the most common treatment-emergent adverse event in healthy subjects treated with ALN-HSD (N=44) was injection site reaction in five patients; all injection site reactions were mild in severity. No treatment-related serious adverse events have been reported in either healthy volunteers or patients with NASH to date. Based on these results, the companies plan to initiate a Phase 2 study in adult patients with NASH in late 2022.
“We are excited to share these initial results, indicating what we believe to be a favorable profile for ALN-HSD and supporting continued clinical development of this investigational medicine, particularly given the significant prevalence and unmet need in NASH – a progressive liver disease and a leading cause of liver transplant,” said Kevin Sloan, Ph.D., Vice President, Development Programs and Program Leader for the ALN-HSD program at Alnylam. “Our RNAi platform is ideally suited for this genetic target. We look forward to reporting detailed results from this study at an upcoming medical congress and to share details of the Phase 2 study design in partnership with our colleagues at Regeneron.”
“The Regeneron and Alnylam collaboration continues to produce compelling clinical and pre-clinical stage therapeutic candidates targeting notoriously hard-to-treat diseases such as NASH and Alzheimer’s,” said Aris Baras, M.D., Senior Vice President and Head of the Regeneron Genetics Center. “By building on each company’s deep expertise in human genetics as well as drug technology and development capabilities, we are progressing ALN-HSD to Phase 2 assessment and are rapidly moving PNPLA3– and CIDEB-targeting therapeutics towards first-in-human studies, resulting in an exciting portfolio of potential future genetic medicines for NASH.”
* The NAFLD Activity Score (NAS) is a widely accepted scoring system developed by the NASH Clinical Research Network for use in clinical trials. The score is based on histological assessment of liver biopsies and is comprised of a sum of steatosis, ballooning, and lobular inflammation component scores.
