Conference Coverage

Multiple therapies for NAFLD and NASH are now in phase 3 clinical trials



– Several potential treatments for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) currently in phase 3 trials show promise in treating these complex disorders.

“When we talk emerging treatments in NASH, focusing on phase 3s [trials], there are really four drugs,” said Stephen Harrison, MD, the medical director of Pinnacle Clinical Research at the annual Digestive Disease Week®. “There’s elafibranor, obeticholic acid (OCA), selonsertib, and cenicriviroc. Each of these have there own phase 3.”

Dr. Stephen Harrison, medical director of Pinnacle Clinical Research

Dr. Stephen Harrison

The phase 3 trials for these drugs have different primary endpoints, an important factor to consider, according to Dr. Harrison.

OCA is one of the promising drugs to treat NASH. It is already approved by the Food and Drug Administration to treat primary biliary cholangitis. In FLINT (The Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial), a phase 2 study, OCA showed promise in treating NASH. In this double-blind, randomized, controlled trial, 141 patients received 25 mg of OCA daily for 72 weeks while another 142 received placebo. By the end of the study, 45% of 110 patients in the OCA group had improved their liver histology, compared with only 21% of patients receiving placebo.

Currently, the REGENERATE trial is evaluating the effects of obeticholic acid on histologic improvement and liver related outcomes in NASH patients. Patients have been randomized to receive either 10 mg of OCA, 25 mg of OCA, or placebo. As of yet, no results have been posted.

Much as he did for trials involving OCA, Dr. Harrison also detailed the results of a phase 2b elafibranor study that led to a registration trial that is currently underway. In Golden 505 (Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis), patients were randomized to receive either GFT505 80 mg, GFT505 120 mg, or placebo. The aim of the study was to identify the percentage of responders with disappearance of steatohepatitis without worsening of fibrosis. Unfortunately, there was no difference between placebo and the treatment groups for this outcome, although a post hoc analysis did reveal that NASH resolved in a higher proportion of the 120-mg elafibranor group, compared with the placebo group (19% vs. 12%, respectively). This also translated into a reduction of 0.65 in liver fibrosis stages in responders, compared with a 0.10 increase in nonresponders (P less than .001).

Now, elafibranor is being further examined in RESOLVE-IT (Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis), but no results have been posted at press time.

Cenicriviroc has followed a similar path, with a phase 2b leading to a phase 3 study.

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