Durect (DRRX)

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DURECT Announces Presentation of Data from a Phase 1b Study of DUR-928 in Nonalcoholic Steatohepatitis (NASH) at The International Liver Congress
Monday 24 April 2017 at 4:01pm


CUPERTINO, Calif., April 24, 2017 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX), a biopharmaceutical company actively developing new therapeutics based on its Epigenetic Regulator Program and proprietary drug delivery platforms, announced that clinical data on DUR-928 were presented at The International Liver CongressTM 2017 (the 52nd annual meeting of the European Association for the Study of the Liver (EASL)) on April 22 in Amsterdam.

"DUR-928 was well tolerated in this study and plasma exposure of the molecule was not significantly increased in NASH patients compared to matched control subjects with normal liver function," stated James E. Brown, D.V.M., President and CEO of DURECT. "Importantly, treatment with a single dose of DUR-928 was associated with a decrease in cell death markers, an improvement of a biomarker of liver function, and decreases in certain biomarkers associated with inflammation."

Phase 1b trial in patients with NASH

The study was a Phase 1b single dose ranging (50 mg and 200 mg), safety and pharmacokinetic (PK) study of orally-administered DUR-928 in two cohorts of biopsy-confirmed NASH patients and matched control subjects (MCS) (matched by age, BMI, and gender) with normal liver function. Both cohorts consisted of 10 NASH patients and 6 MCS.

In both cohorts, DUR-928 was well tolerated overall. There was approximately a 10-30% increase in DUR-928 exposure in NASH patients compared to MCS. A single serious adverse event (shortness of breath), designated as possibly related to study drug, was reported in Cohort 2 in a NASH patient with a prior history of arrhythmia and an ongoing viral infection; no unusual abnormal biochemistry was observed and the symptom spontaneously resolved.

Exploratory biomarker analysis indicated that a single oral dose of DUR-928 resulted in reductions from baseline in the levels of both full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP and IL-18 in NASH patients.

The decrease of full-length CK-18 (a generalized cell death marker) at 12 hours was approximately 33% in the NASH patients in the low dose cohort and approximately 41% in the high dose cohort. The decrease of cleaved CK-18 (a cell apoptosis marker) at 12 hours was approximately 37% in the NASH patients in the low dose cohort and approximately 47% in the high dose cohort.
The decrease in total bilirubin (a liver function marker for which a decrease would be seen as positive) at 12 hours in the NASH patients was approximately 27% in the low dose cohort and approximately 31% in the high dose cohort.
High sensitivity C-Reactive Protein (hsCRP), a marker of inflammation, trended higher at 12 hours in the NASH patients by approximately 3% in the low dose cohort but trended lower by approximately 12% in the high dose cohort.
IL-18, an inflammatory mediator implicated in both liver and kidney diseases, trended lower at 12 hours by approximately 5% in both the low dose cohort and in the high dose cohort.
Collectively, the reduction of these biomarkers, together with results from DURECT's animal and cell culture studies, suggest potential therapeutic activity of DUR-928 in patients with liver disease. However, additional studies, including larger controlled trials, will be required to confirm these findings and to evaluate the safety and efficacy of DUR-928, and there is no assurance that these biomarker effects will be observed in a statistically significant manner, or that DUR-928 will demonstrate safety or efficacy in treating NASH or other liver diseases in larger controlled trials.

The poster that was presented at ILC 2017 will shortly be posted to the "Science & Technologies" section of DURECT's website at www.durect.com.