First Patient Dosed in DUR-928 Study in COVID-19 Patients with Acute Liver, Kidney Injury

DURECT has dosed the first patient in its randomized, double-blind, placebo-controlled, multi-center Phase 2 study to evaluate the safety and efficacy of DUR-928 in hospitalized COVID-19 patients with acute liver or kidney injury. The primary efficacy endpoint is a composite of survival and being free of acute organ failure at Day 28. The company plans to enroll approximately 80 patients in multiple study sites across the U.S.

"We are excited to have begun dosing DUR-928 in this population of hospitalized COVID-19 patients with the additional complications of acute liver or kidney injury. These patients are at risk of multi-organ failure and death, similar to hospitalized patients with AH," said James E. Brown, D.V.M., President and CEO of DURECT. "Based on the positive clinical results of DUR-928 in hospitalized AH patients from our Phase 2a trial and our preclinical data in multi-organ failure models, we believe that DUR-928, in combination with standard of care, has the potential to help these COVID-19 patients."

This Phase 2, randomized, double-blind, placebo-controlled, multi-center study is designed to evaluate safety and efficacy of DUR-928 in COVID-19 patients with acute liver or kidney injury. A total of approximately 80 patients are planned to be enrolled into two study treatment groups in a 3:1 (DUR-928: placebo) ratio. Patients will receive a dose of 150 mg of DUR-928 or placebo by intravenous infusion on day 1 and day 4 in combination with standard of care therapy, which will be determined by the principal investigator (PI) at each clinical trial site. The primary efficacy endpoint is a composite of survival and being free of acute organ failure (free of mechanical ventilation, free of liver failure events and free of renal replacement therapy) at day 28. Patients will be followed for 60 days.

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-COV-2). The rapid spread of the disease has resulted in a pandemic with millions of confirmed cases and hundreds of thousands of deaths worldwide. While most cases result in mild symptoms, including fever, cough and shortness of breath, some rapidly progress into acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Many of these patients experience a rapid elevation of inflammation-inducing signaling molecules (cytokine storm) that trigger acute injuries in multiple organs including the liver and the kidney. Organ injury may also occur in hospitalized COVID-19 patients as the result of other complications of the viral infection. In a study of 1,059 adult cases of confirmed hospitalized COVID-19, 62% of patients presented with at least one elevated liver enzyme. In another study, 36.6% of 5,449 patients admitted with COVID-19 had or developed acute kidney injury (AKI).

DURECT's lead drug candidate, DUR-928, is an endogenous sulfated oxysterol and an epigenetic regulator. It represents a new class of therapeutics with a unique mechanism of action. DUR-928 epigenetically modulates the expression of multiple clusters of master genes that are involved in many important cell signaling pathways, through which it stabilizes mitochondria, reduces lipotoxicity, regulates inflammatory or stress responses, and promotes cell survival.