EASL 2024: DURECT to Present AHFIRM Phase 2b Alcoholic Hepatitis Data

DURECT Corporation, a biopharmaceutical firm dedicated to developing epigenetic therapies for severe health conditions such as acute organ injury and cancer, has been granted a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2024. Scheduled to take place from June 5 to 8 in Milan, Italy, the presentation will delve into the findings from the Phase 2b AHFIRM trial, which examined the safety and efficacy of larsucosterol in treating patients with severe alcohol-associated hepatitis (AH).

The AHFIRM trial was a randomized, double-blind, placebo-controlled, international, multi-center study that included 307 participants with severe AH. It was divided into three arms: standard of care (SOC) with a placebo and supportive care, larsucosterol at a 30 mg dosage, and larsucosterol at a 90 mg dosage. The primary goal was to measure the 90-day mortality rate or the need for liver transplantation in patients treated with larsucosterol compared to those receiving SOC. The key secondary endpoint was survival at 90 days. The trial was conducted across various sites in the U.S., EU, U.K., and Australia.

Alcohol-associated hepatitis is a critical form of liver disease linked to prolonged heavy alcohol consumption, often resulting in severe inflammation and liver cell damage, which can lead to life-threatening complications. Currently, there are no FDA-approved treatments for AH. Historical data indicates high mortality rates for AH patients, with a significant number not surviving beyond 180 days.

Larsucosterol, an endogenous sulfated oxysterol and an epigenetic modulator, works by inhibiting DNA methylation, which can lead to improved cell survival and reduced inflammation. As an inhibitor of DNA methyltransferases, it has the potential to regulate gene expression involved in stress responses and cell survival pathways. This mechanism suggests its potential use in treating acute organ injury and certain chronic diseases.

DURECT is focused on advancing larsucosterol for the treatment of AH, for which it has received Fast Track Designation from the FDA. The company is also exploring its use in metabolic dysfunction-associated steatohepatitis (MASH). DURECT's portfolio includes POSIMIR®, an FDA-approved non-opioid analgesic, which is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in the United States.

The upcoming EASL Congress presentation will be delivered by Mitchell Shiffman, M.D., Director of the Liver Institute of Virginia, Bon Secours Mercy Health, and is set to take place on Saturday, June 8, 2024, from 2:30 PM to 2:45 PM CEST. The findings from the AHFIRM trial are expected to contribute significantly to the understanding and potential treatment of severe AH.