Key results presented include:
- Mean baseline laboratory characteristics and prognostic scores:
- Bilirubin 14.2 mg/dL, (upper limit of normal is 1.2 mg/dL)
- MELD (Model for End-Stage Liver Disease) score 22.3, (≥21 is severe)
- Maddrey's Discriminant Function 53.4 (≥32 is severe AH)
- Drug exposure for DUR-928 (as measured by both AUC and Cmax) was dose proportional and comparable between moderate and severe AH patients.
- Due to the severe liver injury in AH patients, the systemic clearance of DUR-928 was reduced resulting in an approximately 2-fold higher Cmax in these AH patients compared to healthy subjects.
As previously reported, DUR-928 was well tolerated at all doses tested. All patients treated with DUR-928 survived through the 28-day follow-up period. Patients treated with DUR-928 had a statistically significant reduction from baseline in bilirubin at days 7 and 28, and in model of end-stage liver disease (MELD) score at day 28. There was a 100% treatment response rate (as defined by
"We are encouraged by the PK results presented at EASL which demonstrate that DUR-928 was well tolerated at all doses tested in AH patients and contributed to the dose selection in our upcoming Phase 2b AH trial, which we look forward to initiating in the upcoming months," stated
About the DUR-928 Alcoholic Hepatitis Phase 2a Trial
This open-label, dose escalation, multi-center study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of DUR-928 in AH patients following treatment. This included assessing liver biochemistry, biomarkers, and prognostic scores such as the Lille score. Final enrollment included 19 patients with moderate and severe AH, who were administered DUR-928 intravenously at three different doses. Eight patients (four moderate and four severe) were dosed at 30mg, seven patients (three moderate and four severe) were dosed at 90mg and four patients (all severe) were dosed at 150mg. For more information, refer to ClinicalTrials.gov identifier: NCT03432260.
DUR-928: next steps in alcoholic hepatitis
About Alcoholic Hepatitis (AH)
AH is an acute form of alcoholic 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. 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. According to the most recent data provided by the Agency for Healthcare Research and Quality (AHRQ), a part of the US Department of Health and Human Services (HHS), there were over 117,000 hospitalizations for patients with alcoholic hepatitis in 2016. From a recent publication analyzing the mortality and costs associated with alcoholic hepatitis, the cost per patient is estimated at over $50,000 in the first year. Liver transplantation usually involves a long waiting period, a burdensome selection process and a costly procedure over
DURECT Forward-Looking Statement
The statements in this press release regarding clinical development and plans for DUR-928, including initiating a Phase 2b trial of DUR-928 in AH in the second half of 2020, and the potential benefits and uses of our drug candidates, including the potential use of DUR-928 to treat acute organ injuries such as AH and COVID-19 patients with acute liver or kidney injury as well as chronic liver diseases such as NASH, and the use of POSIMIR to treat pain after surgery, 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 are not started or finalized when anticipated, take longer to conduct than anticipated, do not generate similar positive results as generated in earlier clinical or pre-clinical trials, or do not demonstrate the safety or efficacy of DUR-928 in a statistically significant manner, the risk that the FDA will not approve POSIMIR, the risk of disruptions to our business operations resulting from the COVID-19 pandemic, the risk that additional time and resources may be required for development, testing and regulatory approval of DUR-928 or POSIMIR, 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
NOTE: POSIMIR® and SABER® are trademarks of
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Corporate Contact, Mike Arenberg, DURECT, Chief Financial Officer, +1-408-346-1052, firstname.lastname@example.org; Media Contact, Alison Chen, LifeSci Communications, +1-646-876-4932, email@example.com