Pegylated arginine deiminase (ADI-PEG 20), depleting arginine for mesothelioma

Polaris initiates ADI-PEG 20 Phase 2 trial in patients with malignant mesothelioma

Published on March 19, 2011   Polaris Group announced today the enrollment of the first patient in a Phase 2 clinical trial of ADI-PEG 20 (pegylated arginine deiminase), the company's novel enzyme-based treatment for malignant mesothelioma. This randomized trial, called "ADAM" (Arginine Deiminase And Mesothelioma), will evaluate the treatment efficacy of ADI-PEG 20 as a single agent compared to the best supportive care. The primary endpoint of the study is progression free survival. Peter Szlosarek, M.D., Ph.D., of the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, is the lead investigator of the study. "It is with great anticipation that the ADAM trial has opened at Barts and other cancer centers in the U.K., including hospitals in Belfast, Cambridge, Hull, Manchester and Southampton," said Dr. Szlosarek. "We are pleased to be joining Polaris Group in exploring the potential benefits of ADI-PEG 20 in treatment of different cancers." Malignant mesothelioma is a cancer of the lungs that frequently occurs in people who have been exposed to asbestos. The disease is usually diagnosed two to three decades after prolonged exposure and when it has generally spread beyond the stage for successful surgical treatment.  The prognosis for patients with late stage malignant mesothelioma is poor with a median survival of less than one year. Polaris Group scientists and colleagues have been investigating the metabolic enzyme argininosuccinate synthetase (ASS) and its presence or absence in relationship to growth of normal cells and tumor cells.  ASS is required for the production of arginine, an amino acid needed for growth and replication of cells. Normal cells have normal levels of ASS and can produce sufficient arginine for their own growth and survival. However, many types of tumor cells cannot make their own arginine due to a deficiency in ASS and, therefore, must obtain it from external sources. ADI-PEG 20 depletes the external supply of arginine, causing these tumor cells to die.