Galmed Pharmaceuticals Ltd. (NASDAQ: GLMD), a clinical-stage biopharmaceutical company focused on the development of Aramchol™, an oral, once-daily, liver-targeted SCD1 modulator, for the treatment of non-alcoholic steatohepatitis (NASH), announced top-line, 52-week results from the global Phase 2b ARREST study. In the ARREST study, patients underwent MRS and biopsy at baseline and week 52, which were centrally read, blinded to treatment allocation. The primary endpoint of the study was the change from baseline to end of study in liver triglycerides ratio as measured by MRS (Aramchol 600mg vs. placebo). Secondary endpoints, demonstrated through biopsy, included fibrosis improvement by at least one stage or more without worsening of NASH (defined by an increase of inflammation and or ballooning) and NASH resolution (defined by ballooning score 0 and inflammation score 0-1 at termination) without worsening of fibrosis. Other secondary endpoints included improvement (2 points or more) in NASH activity index, as measured by NAS or SAF, without worsening fibrosis and change in baseline to week 52/termination in ALT (U/L).
"Some studies have shown an effect on NASH and some on fibrosis, while this study has shown an effect on both. Concomitant ALT reduction strengthens the histological findings," said Prof. Vlad Ratziu, M.D., Principal Investigator of the ARREST study and Professor of Hepatology, Sorbonne Université and Hospital Pitié – Salpêtrière, Paris, France. "Aramchol 400mg is probably sufficient for fat reduction but, biologically, a higher dose is needed for achieving more stringent histological endpoints such as NASH resolution and fibrosis reversal. NASH is a chronic disease with complex comorbidities and Aramchol's favorable safety and tolerability profile support long-term treatment," concluded Prof. Ratziu.
"Results seen in the ARREST 52-week study are comparable to other one-year trials recently published or presented in the NASH space. Pre-clinical studies had demonstrated that Aramchol has a unique mechanism of action that addresses both the metabolic dysfunction and fibrosis directly, and these mechanisms have been validated by findings in the ARREST study," said Prof. Scott Friedman M.D., Dean for Therapeutic Discovery and Chief Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. "Specifically, data from my laboratory submitted to an upcoming conference confirm by transcriptomic analysis a broad anti-fibrotic effect of Aramchol in fibrogenic hepatic stellate cells, which is complementary to the data seen in this Phase 2b, biopsy-based clinical study. In my view, these results, together with its safety and tolerability, place Aramchol among the leading frontline therapeutic candidates under investigation for NASH."
"These are exciting data which demonstrate that 600mg of Aramchol improves disease activity, fibrosis and progression to cirrhosis which in the long term may translate to meaningful clinical improvement," said Prof. Arun Sanyal, M.D., Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University and Co-Chair of the Liver Forum at the Forum for Collaborative Research at the University of California, Berkeley, School of Public Health. "Furthermore, the dose dependency of the effects and the fact it was a global study represents the clinical reality of the global NASH pandemic and provides indications that these results are likely to be reproduced in a pivotal phase 3 trial."