Benzinga | Jun 23, 2021 09:03AM EDT

DURECT Highlights Presentation Of Added Clinical Data From DUR-928 Phase 1b Trial In NASH, Phase 1 Trial In Hepatic Impairment At Int'l. Liver Conference Jun. 23-26

DURECT Corporation (NASDAQ:DRRX) today announced the presentation of additional clinical data from a DUR-928 Phase 1b trial in non-alcoholic steatohepatitis (NASH) and a Phase 1 trial in subjects with hepatic impairment (HI) as part of two posters at the 2021 International Liver Conference (EASL) being held virtually June 23-26, 2021.

"We are pleased to report additional signals of potential efficacy from our Phase 1b NASH trial of DUR-928, our lead epigenetic regulator," said James E. Brown, D.V.M., President and CEO of DURECT. "The roughly 20% median reduction from baseline of HOMA-IR, an important indicator of insulin resistance, observed after only 4 weeks of daily oral administration at the 50 mg and 150 mg dose levels, is similar to the level of reductions seen in longer term studies of several well-established diabetes therapeutics. In addition, the Phase 1 trial in subjects with moderate and severe hepatic function impairment further demonstrates DUR-928's safety and potential efficacy profile in subjects with serious liver disease. We continue to make progress opening new clinical trial sites and enrolling patients in our ongoing AHFIRM Phase 2b trial in alcohol-associated hepatitis (AH) patients while we determine next steps for DUR-928 in NASH and explore additional potential acute and chronic indications."

Poster #1198 entitled "Efficacy Signals of 4-Week Oral DUR-928 in NASH Subjects," presented by Eric Lawitz, M.D., Vice President, Scientific and Research Development, Texas Liver Institute, disclosed additional potential efficacy signals from DURECT's Phase 1b clinical study of orally administered DUR-928 in nonalcoholic steatohepatitis (NASH) patients. Key highlights include:

* Improvement from baseline in insulin resistance as assessed by the homeostatic model assessment (HOMA-IR). Subjects in the 50 mg and 150 mg groups had 22% and 18% median reductions (not statistically significant) of HOMA-IR from baseline respectively after 4 weeks of daily oral dosing of DUR-928. Subjects in the 600 mg group did not show a change in HOMA-IR.

* Improvement from baseline in liver stiffness, assessed by transient elastography (TE), magnetic resonance elastography (MRE) and the liver fibrosis marker pro-C3.

* Previously reported data showed improvement from baseline in: liver enzymes such as ALT, AST and GGT and improvements in serum lipid profiles such as LDL-C, non-HDLC and triglycerides; liver fat by MRI-PDFF imaging; and biomarkers of liver health, such as CK-18, a cell death biomarker, certain of which were statistically significant improvements.

* Safety profile: DUR-928 was safe and well tolerated by all subjects in the study.

Data highlights from Poster #668 entitled "Safety and Pharmacokinetics of DUR-928 in Hepatic Function Impaired Subjects," presented by Jaymin Shah, Ph.D., Executive Director, Clinical Pharmacology and Pharmacokinetics at DURECT, included:

* Safety profile: DUR-928 was safe and well-tolerated by all moderate and severe hepatic impairment (HI) subjects with no adverse events and no dose-limiting toxicity reported throughout the study.

* Pharmacokinetics: As expected, clearance of DUR-928 was decreased in HI subjects compared to matched control subjects with normal hepatic function, leading to a 4-10 fold higher drug exposure (Cmax and AUC) in HI subjects depending on the severity of HI.

* Initial efficacy signals: A single oral dose of 200 mg of DUR-928 in subjects with HI resulted in statistically significant median reductions from baseline of the apoptosis biomarker M30 (cCK-18) at 12 hours post-dose.

Copies of the posters will be available on DURECT's corporate website here at the conclusion of the conference.