“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
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
The poster that was presented at ILC 2017 will shortly be posted to the “Science & Technologies” section of
NOTE: POSIMIR®, SABER®, and ORADUR® are trademarks of
DURECT Forward-Looking Statement
The statements in this press release regarding the potential benefits and uses of our drug candidates, including the potential use of DUR-928 to treat NASH, other disorders of the liver, acute organ injury, kidney diseases or psoriasis or other inflammatory conditions, the potential use of POSIMIR and REMOXY ER to treat pain, and potential markets for our product candidates are forward-looking statements involving risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, the risks that future clinical trials of DUR-928 do not replicate results reported here or do not demonstrate the safety or efficacy of DUR-928 in a statistically significant manner, the risk of delays in the commencement, enrollment or completion of clinical trials, the potential failure of clinical trials to meet their intended endpoints, the risk of adverse decisions by regulatory agencies or delays and additional costs due to requirements imposed by regulatory agencies, additional time and resources that may be required for development, testing and regulatory approval of DUR-928, potential adverse effects arising from the testing or use of our drug candidates, our potential failure to maintain our collaborative agreements with third parties or consummate new collaborations and risks related to our ability to obtain capital to fund operations and expenses. Further information regarding these and other risks is included in
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Matt Hogan, Chief Financial Officer, DURECT, 408-777-4936 or Matthew Duffy, Managing Director, LifeSci Advisors, 212-915-0685