DURECT's Larsucosterol Shows Promise in Alcohol-Associated Hepatitis Treatment
Key Insights
DURECT Corporation's larsucosterol demonstrates potential in treating alcohol-associated hepatitis (AH) by reducing mortality rates in U.S. patients.
A Phase 3 trial, agreed upon with the FDA, will assess larsucosterol's efficacy with a 90-day survival primary endpoint, aiming for topline data within two years.
Larsucosterol targets DNA methyltransferases, epigenetic enzymes linked to hypermethylation in AH, offering a novel approach to managing the condition.
DURECT CorporationView company profile is advancing its lead drug candidate, larsucosterolSearch drug, for the treatment of alcohol-associated hepatitisSearch disease (AHSearch disease). The company will present additional data from its Phase 2b AHFIRM trial at The Liver Meeting 2024, showcasing the potential of larsucosterol and supporting the design of the upcoming Phase 3 trial.
The FDA has granted larsucosterolSearch drug Fast Track and Breakthrough Therapy designations for AHSearch disease, underscoring the urgent need for effective therapies. The company held a Type B meeting with the FDA, reaching an agreement on key aspects of the Phase 3 trial design.
Phase 3 Trial Design
The Phase 3 trial is designed as a randomized, double-blind, placebo-controlled, multi-center study in the U.S. It will enroll approximately 200 patients with severe AHSearch disease, randomized 1:1 to receive either larsucosterolSearch drug (30 mg) or placebo, in addition to standard of care, with or without methylprednisolone at the investigator's discretion. The primary outcome measure is 90-day survival, with topline results expected within two years of trial initiation.
James E. Brown, D.V.M., President and CEO of DURECT, stated, "We believe the primary endpoint of 90-day survival is clinically meaningful and provides the greatest probability of success based on the AHFIRM data."
AHFIRM Trial Data
Data from the Phase 2b AHFIRM trial demonstrated a compelling efficacy signal for larsucosterolSearch drug. In U.S. patients, both the 30 mg and 90 mg doses of larsucosterol reduced mortality at 90 days by 57% (p=0.014) and 58% (p=0.008), respectively, compared to placebo.
Norman Sussman, M.D., FAASLD, Chief Medical Officer of DURECT, noted, "Based on our Phase 2b AHFIRM data, we believe larsucosterolSearch drug has the potential to save the lives of tens of thousands of patients yearly who currently have very limited options."
About Larsucosterol
LarsucosterolSearch drug is an endogenous sulfated oxysterol and an epigenetic modulator. It inhibits DNA methyltransferasesSearch term (DNMT1Search term, DNMT3aSearch term, and 3b), which are elevated and associated with hypermethylation in AHSearch disease patients. By inhibiting DNA methylation, larsucosterol modulates the expression of genes involved in cell signaling pathways, potentially improving cell survival, reducing inflammation, and decreasing lipotoxicity.
The Need for New AH Treatments
AHSearch disease is an acute form of alcohol-associated liver disease characterized by severe inflammation and liver cell damage. There are no FDA-approved therapies for AH, and mortality rates remain high. A retrospective analysis showed overall mortality from AH was 26% at 28 days, 29% at 90 days, and 44% at 180 days. While liver transplantation is an option, it is limited by organ availability and high costs, averaging over $875,000 per transplant.