DUR-928 is an investigational product and has not been approved by the FDA for marketing in the U.S. for any indication.
DURECT is conducting a Phase 2a clinical trial of intravenously administered DUR‑928 in patients with alcoholic hepatitis (AH). This is an open label, dose escalation (30 mg, 90 mg, and 150 mg), multi-center U.S. study that is enrolling patients with moderate and severe AH. Dose escalation may occur following review of safety and pharmacokinetics (PK) results of the prior dose level by a Dose Escalation Committee. Target enrollment for the study is 4 moderate and 4 severe patients per dose group. The objectives include assessment of safety, PK, and pharmacodynamic signals, including liver chemistry and biomarkers.
As reported May 8, 2019 in a news release and key opinion leader conference call, the first 10 AH patients dosed with DUR‑928 demonstrated significant reductions from baseline in serum bilirubin levels and MELD scores compared with historical controls. DUR‑928 was well tolerated and PK parameters were not affected by the severity of the disease.
Lille scores, which are used in clinical practice to evaluate the responses and prognosis of AH patients after 7 days of corticosteroid treatment, were also assessed in these patients. Patients with a Lille score below 0.45 have an 85% 6‑month survival rate, whereas those with Lille scores of above 0.45 have only a 25% 6‑month survival rate.1 The median Lille score for the nine DUR‑928-treated AH patients who returned for their Day 7 visit was 0.04 (range: 0.01 to 0.19). The median Lille score among a cohort of 15 patients treated at the University of Louisville (UL) with either supportive care or supportive care plus corticosteroids (historical controls) was 0.41 (range: 0.02 to 0.96).2
The graphs below show individual patient Lille scores (calculated on Day 7) plotted as a function of their initial MELD scores.3
MELD score (Day 0) and Lille response (Day 7)
Alcoholic liver disease (ALD) is a disorder characterized by progressive inflammatory liver injury associated with long-term heavy intake of alcohol. It manifests on a spectrum that ranges from mild liver injury to severe impairment of liver function. Alcoholic hepatitis (AH) is an acute, potentially life-threatening form of ALD for which no effective therapeutics are available. The prevalence of AH is believed to be 10%-35% of heavy drinkers.1 There were over 320,000 hospitalizations related to AH in 2010, and the hospitalization costs amounted to nearly $50,000 per patient.2 ALD is a leading cause of liver transplants in the U.S.3, and the cost of a liver transplant exceeds $800,000.4 Alcohol use disorder (AUD) as a whole affects 15.1 million adults (6.2%) in the U.S.5
DURECT currently holds the worldwide development and commercialization rights to DUR-928 and other molecules identified as part of the Epigenetic Regulator Program.
There are risks and uncertainties associated with our business. Please see our most recent SEC filings (10-K or 10-Q) for a complete description of these risks and uncertainties, which are incorporated herein by reference.