A Phase 2b trial of a promising drug to treat alcohol-related hepatitis recently completed its all-patient study protocol and results are now expected to be released by the end of 2023.
DURECT recently announced that the last patient completed the final visit in the AHFIRM trial, a Phase 2b, randomized, double-blind, placebo-controlled analysis of larsucosterol in patients with severe alcohol-related hepatitis. The company currently expects to have efficacy and safety data from a 300-patient mid-stage trial in the coming months.
during an interview HCP live broadcastAHFIRM investigator Nancy Reau, M.D., Richard B. Capps Chair in Hepatology at RUSH School of Medicine, discusses the mechanisms of action supporting the potential benefits of larsucosterol in treating alcohol-related hepatitis—a growing problem in the United States but one with little clinical use has been solved.
“Alcohol is a toxin, but a massive immune response to this damage appears to cause liver damage,” Luo explained. “This is true for many liver injuries—whether it’s hepatitis C, viral hepatitis or fatty liver disease—many times the damage caused by the disease itself is not as great as the damage caused by the response to the disease.”
Larsucosterol is a drug with observed epigenetic modulatory effects on the inflammatory response described in alcohol-related hepatitis.
“We tell (patients and clinicians) a lot that what this drug does is it reprograms it so that there’s not as much cell damage and cell dysfunction, so it seems to truncate or improve cell death, thereby improving survival,” “Reau said. “This would hopefully attenuate the immune response or the response within the liver.”
Reau further highlighted this “rather complex agent,” mentioning its function in lipid biosynthetic and fat deposition pathways. Nonetheless, timing is critical in this patient population.
“Our hope is to identify people with alcoholic hepatitis as early as possible,” Luo said. “If they are really sick and have severe kidney dysfunction, we know that these people are already too sick to really benefit from any other treatment other than a transplant if a transplant is appropriate for them. “We also Do not want to give any medicine to people who are likely to improve their condition through abstinence and nutrition. “
The AHFIRM trial boils down to treating patients “whose disease is likely to get worse without intervention, but not to the point where they need a liver transplant or have no options to cut off the disease” and then see if this drug might help Prevent disease progression. “