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Phase 2b data from the AHFIRM trial is anticipated soon. Reau discusses what the agent may show in treating alcohol-associated hepatitis.
A phase 2b trial for a promising agent to treat alcohol-associated hepatitis recently completed its full-patient study protocol and is now projecting outcome findings to be published before the end of 2023.
DURECT Corporation recently announced that the last patient completed their last visit in the AHFIRM trial, a phase 2b, randomized, double-blind, placebo-controlled analysis of larsucosterol for the treatment of patients with severe alcohol-associated hepatitis. The company now anticipates to have efficacy and safety data reported from the mid-stage, 300-patient trial in the coming few months.
In an interview with HCPLive, AHFIRM investigator Nancy Reau, MD, Richard B. Capps Chair of Hepatology at RUSH Medical College, discussed the mechanism of action supporting larsucosterol’s potential benefit in treating alcohol-associated hepatitis—a growing issue in the US that is met with few clinical resolves.
“Alcohol is a toxin, but it's a lot of immune reaction to that injury that seems to lead to the liver damage,” Reau explained. “And that's true for a lot of liver injuries—whether it's hepatitis C, viral hepatitis, or fatty liver disease, lots of time the disease itself isn't causing as much damage as the reaction to that disease.”
Larsucosterol is an agent with observed epigenetic modulation effects that impact the said inflammatory response of alcohol-associated hepatitis.
“We tell (patients and clinicians) a lot that this agent works on reprogramming so that there's not as much cell injury and cell dysfunction, so that it seems to truncate or ameliorate cell death, which improves survival,” Reau said. “And that is going to hopefully blunt that immune response or that reaction within the liver.”
Reau further highlighted the “pretty sophisticated agent,” mentioning its function on lipid biosynthesis and fatty deposit pathways. All the same, timing is key for this patient population.
“The hope is identifying individuals with alcoholic hepatitis at an early enough time point,” Reau said. “If they're really, really sick and have significant renal dysfunction, we know that that population is already too sick to really benefit from anything other than transplant if transplant is appropriate for them. We also don't want to give any agent to someone who's very likely to improve on their own with abstinence and nutrition.”
The AHFIRM trial boils down to treating patients where “they're likely to become more ill without intervention, but not so ill yet that they need a liver transplant or that there isn't any option to truncate the disease, and then to see if this agent might be beneficial in helping to prevent progression.”