Benzinga | Nov 13, 2020 09:02AM EST

DURECT Reports Added Safety Data, Efficacy Signals From Phase 1b Trial Of DUR-928 In NASH Patients At The Liver Meeting Digital

DURECT Corporation (NASDAQ:DRRX) today presented additional safety data and efficacy signals from its Phase 1b clinical trial of DUR-928 in nonalcoholic steatohepatitis (NASH) patients in a poster presentation at The AASLD Liver Meeting Digital Experience (tm) (TLMdX) 2020.

"The additional safety and efficacy data presented, including improvements in multiple biomarkers of liver health such as a significant reduction in cytokeratin-18 among the patients who also experienced at least a 10% reduction in liver fat, continue to strengthen the promising profile of DUR-928 for NASH," stated Eric Lawitz, M.D., Texas Liver Institute, University of Texas Health San Antonio and principal investigator of the study. "Together with previously reported overall global reduction from baseline of liver enzymes, liver fat, stiffness as measured by imaging and serum lipids, this additional biomarker data suggests that epigenetic modulation by DUR-928 is worthy of further study in NASH patients."

James E. Brown, D.V.M., President and CEO of DURECT, added, "The safety and efficacy profiles demonstrated with DUR-928 not only in this NASH trial but in our Phase 2a trial in alcoholic hepatitis, demonstrate potential of this epigenetic regulator to treat multiple acute organ injury and chronic liver diseases. We look forward to continuing the evaluation of DUR-928 in our clinical studies and potentially bringing a life-saving treatment option to patients in need."

Data presented at The Liver Meeting further demonstrated that DUR-928 was well tolerated at all three doses (50mg, 150mg, and 600mg) with no serious adverse events reported.

Improvements in Biomarkers Data Summary (Day 28 vs Baseline)

% change from baseline at the end of dosing (median at day 28)

Biomarker Daily Dose (mg)

50 150 600

Cytokeratin 18 M30 -14.6-8.6 -16.1

Cytokeratin 18 M65 -18.1-9.9 -35.0

C Reactive Protein -13.9-11.81.7

Plasminogen Activator-13.5-13.7-8.2 Inhibitor-1

Interleukin 1 Beta -0.1 -0.6 -0.2

Interleukin 6 -6.0 1.7 5.4

Interleukin 12 0.0 0.0 0.0

Interleukin 17 -1.3 -16.4-0.8

Interleukin 18 -8.9 -5.0 -2.1

Tumor Necrosis Factor-3.2 -2.9 -7.9

Bile Acid 0.0 0.0 1.6

Adiponectin -1.6 -3.8 3.9

Adiponectin, HMW 0.0 1.0 1.0

Biomarker Data Along With Previously Reported Improvements in Liver Enzymes, Imaging and Serum Levels (Day 28 vs Baseline)

* Indicates p-value <0.05; ** indicates p < 0.01; *** indicates p <0.001

Patients with ? 10% All Subjects Reduction in

Median MRI-PDFF

at Day 28 50 mg QD 150 mg 300 mg 150 mg 300 mg QD BID 50 mg QD QD BID (n= 21-23) (n= (n= (n=9) (n=8) (n=9) 20-21) 20-21)

ALT -16%* -10% -17%*** -21%** -19%* -32%***LiverEnzymes AST -14% -9% -18%** -24%** -21% -39%***

GGT -6% -1% -8%* -13%*** -16%* -14%

MRI-PDFF -7% -7% -4% -18%*** -19%*** -23%***Imaging FibroScan -10%** -9% -1% -7% -9%** -9%

LDL-C -6% -11%* -7% -7% -11% -8%*SerumLipids Non-HDL-C -8% -5% -1% -10% -8%* -12%*

Triglycerides -13%* -3% -2% -9% 0% -8%

CK-18, M30 -14.6% -8.6% -16.1% -22.8%*** -3.8% -42.1%*Biomarkers CK-18, M65 -18.1% -9.9% -35.0% -28.1%*** -8.7% -55.8%*

ALT (alanine aminotransferase); AST (aspartate aminotransferase); GGT (gamma-glutamyl transferase); MRI-PDFF (Magnetic Resonance Imaging - Proton Density Fat Fraction) is a non-invasive measure of the proportion of liver tissue which is composed of fat; FibroScan is a specialized ultrasound machine that measures the stiffness of liver tissue. LDL-C ( Low-Density Lipoprotein -- Cholesterol); Non-HDL-C (Total cholesterol excluding High-Density Lipoprotein-Cholesterol); QD (once a day); BID (twice a day); CK-18 (cytokeritin 18)

Additionally, in subjects with baseline triglyceride (TG) levels ?200mg/dL (n=16), there was a 24% reduction at the end of the 4-week dosing period (p<0.01).