First Patient Dosed in DUR-928 Study for Severe Alcohol-Associated Hepatitis

DURECT has dosed the first patient in its AHFIRM randomized, double-blind, placebo-controlled, multi-center Phase 2b study to evaluate the safety and efficacy of DUR-928 in severe alcohol-associated hepatitis (AH) patients.

"We are excited to have begun dosing severe AH patients in the AHFIRM trial. There are no approved therapies indicated for treatment of AH and the average mortality rate in AH clinical trials at 90 days after admission to the hospital is 29%," said James E. Brown, D.V.M., President and CEO of DURECT. "In our completed Phase 2a AH trial, all 19 patients dosed with DUR-928 survived the 28-day study period. In this much larger, placebo-controlled Phase 2b AHFIRM trial, we are evaluating DUR-928's lifesaving potential in severe AH patients at 90 days compared to a control group that will receive placebo and standard of care. We believe that demonstration of a robust survival benefit in this trial may support an NDA filing."

AHFIRM is a Phase 2b clinical trial evaluating the potential life-saving capacity of DUR-928 in patients with severe AH. AHFIRM is a randomized, double-blind, placebo-controlled, international, multi-center study to evaluate the safety and efficacy of DUR-928 in approximately 300 patients with severe AH. The study will be comprised of three arms of approximately 100 patients each: (1) DUR-928 (30 mg); (2) DUR-928 (90 mg); and (3) Placebo plus standard of care (SOC). SOC may include the use of methylprednisolone, a corticosteroid, at the discretion of the treating physician. Patients will receive an intravenous (IV) dose of DUR-928 or placebo (sterile water) on day 1 and a second IV dose on day 4 if they are still hospitalized. The primary outcome measure will be 90-day survival rate for patients treated with DUR-928 compared to those treated with placebo plus SOC. Secondary endpoints include 28-day survival, the rate of adverse events, Lille and MELD (prognostic scores), and time in the intensive care unit. The Company is targeting 40-50 clinical trial sites in the US and Europe.

Alcohol-Associated Hepatitis (also called Alcoholic Hepatitis or AH) is an acute form of alcohol-associated liver disease (ALD) associated with long-term heavy intake of alcohol, and often occurs after a recent period of increased alcohol consumption. AH is typically characterized by recent onset jaundice and hepatic failure. According to the Agency for Healthcare Research and Quality (AHRQ), a part of the US Department of Health and Human Services (HHS), there were over 122,000 hospitalizations for patients with AH in 2017. From a recent publication analyzing the mortality and costs associated with AH, the cost per patient is estimated at over $50,000 in the first year. ALD is one of the leading causes of liver transplants in the U.S., costing over $800,000 per patient. An analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days after admission.

DURECT's lead drug candidate, DUR-928, is an endogenous sulfated oxysterol and an epigenetic regulator. It represents a new class of therapeutics with a unique mechanism of action. DUR-928 epigenetically modulates the expression of multiple clusters of master genes that are involved in many important cell signaling pathways, through which it stabilizes mitochondria, reduces lipotoxicity, regulates inflammatory or stress responses, and promotes cell survival.