- 1Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, West Palm Beach, Florida, 33401, USA.
- 2University of South Florida, Taneja College of Pharmacy, Tampa, Florida, USA.
Objective: To describe the mechanism, efficacy, and safety of novel agents that have reached phase 3 clinical trials for the treatment of biopsy-proven non-alcoholic steatohepatitis (NASH).
Data sources: A literature search was conducted using the PRISMA guidelines of MEDLINE databases (1990 to October 2020) with the following MeSH terms: NASH, non-alcoholic liver disease, fatty liver, liver diseases, steatohepatitis, liver fibrosis; combined with obeticholic acid, FXR agonist, cenicriviroc, CCR5 receptor antagonist, elafibranor, PPAR, selonsertib, ASK-1 inhibitor, resmetirom, THR-beta receptor, Arachidyl amido cholanoic acid (Aramchol™), and SCD-1 modulator. Results were verified via clinicaltrials.gov, Google Scholar, and Google.
Study selection and data extraction: Articles were included if the medications of interest had ongoing or completed phase 3 trials in biopsy-proven NASH with outcomes directly related to NASH resolution. Eleven studies were identified involving obeticholic acid (OCA), elafibranor, cenicriviroc, Aramchol, and resmetirom.
Data synthesis: Two agents have reported data from phase 3 trials: OCA and elafibranor. OCA demonstrated safety and efficacy in NASH with a primary end point of improvement or NASH resolution; a new drug approval has been submitted. Elafibranor failed to show efficacy in NASH in the preliminary report from the RESOLVE-IT trial, however the study is being extended to reassess outcomes. The remaining agents demonstrated positive results in phase 2b studies and have initiated phase 3 trials.
Discussion: With projections for increased prevalence of patients with NASH and the current lack of treatment options, novel agents with targeted mechanisms could potentially change the treatment landscape. The manufacturer of OCA is first to submit a new drug application for the treatment of NASH.
Conclusion: These novel agents may fill a pharmacotherapy gap in patients with NASH and possibly prevent progression to advanced liver disease.