Hepion Pharmaceuticals Announces Initiation of Phase 2b ASCEND-NASH Trial

Hepion Pharmaceuticals, Inc. recently announced it has screened the first subject in the ASCEND-NASH clinical trial. The trial is being conducted at up to 121 sites in seven countries, with 85 of the sites located within the US.

ASCEND-NASH is a Phase 2b, randomized, multi-center, double-blinded study to evaluate the safety and efficacy of rencofilstat in 336 subjects dosed for 12 months. Subjects included in the trial will be either F2 or F3 biopsy-confirmed, with enrollment of F3 subjects of at least 60%, to focus on NASH subjects with more advanced fibrosis. Subjects will receive either placebo or rencofilstat, administered orally once daily at doses of 75, 150, or 225 mg (n=84 subjects/cohort). Endpoints will evaluate improvements in both fibrosis and steatosis, with the overall study primary endpoint being an improvement of fibrosis score by one point without a worsening of steatosis, or an improvement of steatosis without worsening of fibrosis. Although the main trial endpoint is histologic and determined by changes in the biopsy, numerous other non-invasive markers (NIM) will be assessed, including NASH efficacy biomarkers, magnetic resonance elastography (MRE), and multiomics (eg, proteomics and transcriptomics).

“ASCEND-NASH represents the first time that rencofilstat is being studied in a biopsy confirmed-trial,” said Todd Hobbs, MD, Hepion’s Chief Medical Officer. “We anticipate full enrollment in 12-to-14 months, as this is a large and rigorously controlled trial with a 60-day screening period including multiple laboratory analyses, Fibroscan evaluation, liver biopsy, and MRE. We will also be following the US FDA-recommended utilization of a three-panel consensus to read all liver biopsies. As the study advances, our independent Data and Safety Monitoring Board will conduct two interim analyses. The first review will occur when one-third of study subjects have passed the 6-month evaluation, and the second DSMB review will occur when one-third of subjects have completed the study and have had a final biopsy. Additionally, we received Fast Track designation from the FDA in November of 2021; this allows for the submission of study reports as they are obtained, as well as more frequent engagement with the Agency, which should provide for smoother transition from Phase 2b to Phase 3.”

“Initiation of screening in our Phase 2b ASCEND-NASH clinical trial represents a significant step forward for our company,” added Robert Foster, PharmD, PhD, Hepion’s Chief Executive Officer. “For quite some time, our team has been busy setting the stage for this major clinical trial. Our efforts have focussed on ongoing optimization of drug manufacturing and product formulation; packaging; qualification of trial sites; and engagement with contract research organizations and regulatory agencies around the world. While these activities are time- and resource-intensive, it is gratifying to now see them culminate in the initiation of subject screening.”

Dr. Foster continued, “Finally, our goal is to create an ecosystem built around rencofilstat as the core asset. To that end, we are utilizing our proprietary AI-POWR tools to explore ways to create companion diagnostics to help identify which subjects may best respond to rencofilstat. We anticipate this approach of bundling rencofilstat with companion diagnostics will be advantageous when conducting future clinical trials, and developing a commercial strategy.”

The company’s lead drug candidate, rencofilstat, is a potent inhibitor of cyclophilins, which are involved in many disease processes. Rencofilstat is currently in clinical-phase development for the treatment of NASH, with the potential to play an important role in the overall treatment of liver disease – from triggering events through to end-stage disease. Rencofilstat has been shown to reduce liver fibrosis and hepatocellular carcinoma tumor burden in experimental models of NASH, and has demonstrated antiviral activities towards HBV, HCV, and HDV through several mechanisms, in nonclinical studies. In November 2021, the US FDA granted Fast Track designation for rencofilstat for the treatment of NASH. That was followed in June 2022 by the FDA’s granting of Orphan Drug designation to rencofilstat for the treatment of HCC.

Hepion has created a proprietary AI platform, called AI-POWR, which stands for Artificial Intelligence – Precision Medicine; Omics (including genomics, proteomics, metabolomics, transcriptomics, and lipidomics); World database access; and Response and clinical outcomes. Hepion intends to use AI-POWR to help identify which NASH patients will best respond to rencofilstat, potentially shortening development timelines and increasing the delta between placebo and treatment groups. In addition to using AI-POWR to drive its ongoing NASH clinical development program, Hepion intends to use the platform to identify additional potential indications for rencofilstat to expand the company’s footprint in the cyclophilin inhibition therapeutic space.