Conatus Pharmaceuticals Inc. and the University of Alberta announced today the treatment of the first patient in an investigator-initiated islet cell transplant Phase I/II trial of emricasan (IDN-6556), a pan-caspase inhibitor. The objective of the trial is to determine safety, achievement and maintenance of insulin independence and to obtain preliminary data on the efficacy of emricasan to maintain adequate immunological protection against both allo- and autoimmunity of islet cell transplant recipients. The sponsor of the trial is the University of Alberta and the principal investigator is A. M. James Shapiro, M.D., Ph.D.
"Preclinical studies support the use of a pan-caspase inhibitor therapy to broaden the availability of clinical islet transplantation. Enhancing islet engraftment post-transplant should prolong graft longevity, resulting in a more quiescent immunological state and thereby enhancing long-term rates of insulin independence. Inhibition of islet apoptosis in the immediate post-transplant period may reduce the amount and intensity of anti-rejection therapy, accelerating 'accommodation' and drug minimization. If this could be achieved, or if stable immunological tolerance was enhanced through emricasan treatment, islet transplantation would be potentially safer and therefore more available to a broader spectrum of patients with type 1 diabetes," said Dr. Shapiro. "Over 750 islet transplantations are now carried out each year in 30 active centers worldwide. Diabetologists, funding organizations and regulatory agencies recognize islet transplantation as an effective therapy to prevent episodic hypoglycemia, correct glycated hemoglobin and reduce risk of secondary diabetic complication."
"As Conatus pursues the development of emricasan on our own in liver disease, I am pleased to support new treatment paradigms in diabetes. If the results in humans are similar to the preclinical data, many more patients will benefit from islet cell transplantation," said Steven J. Mento, President and Chief Executive Officer of Conatus Pharmaceuticals.
The trial will be conducted in two sequential pilot study groups of six patients each with two different dosages of emricasan for 14 days. Once optimal dosing has been determined from these pilot studies, the next proposed study would be a randomized, placebo-controlled study to explore the safety and efficacy of emricasan combined with other islet transplant treatment medications.
Emricasan is a novel small molecule inhibitor of activated caspases. Caspases are enzymes responsible for executing apoptotic pathways, or programmed cell death and are also involved in processing cytokines involved in inflammation. Conatus is planning Phase 3 clinical trials early next year to test emricasan as a treatment in patients for acute liver failure with underlying cirrhosis, and in patients with liver fibrosis. Emricasan has shown specificity in assays measuring caspase inhibition, and reduced apoptosis in a variety of cellular assays. It also demonstrated efficacy in a number of preclinical models of liver disease and islet transplantation as well as in models of damage to other organ systems. Positive Phase 2 data in a 12-week study in patients with chronic Hepatitis C virus (HCV) infection have indicated that the oral formulation of emricasan was well tolerated, and significantly improved key markers of liver damage as early as 7 days after initiation of therapy.
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