Piritrexim (ILEX Oncology).

ILEX Oncology is developing the dihydrofolate reductase inhibitor, piritrexim (discovered originally by Burroughs Wellcome), for the potential treatment of cancer. It is in phase II clinical trials for malignant fibrous histiocytoma. ILEX conducted phase II clinical trials in the US and Europe with piritrexim in bladder cancer patients; however, development for this indication was discontinued in the third quarter of 1998 due to lack of efficacy. The company also initiated phase III trials in early 1997 for the treatment of AIDS-related Kaposi's sarcoma, but no further development for this indication has been reported since that time. Piritrexim was discovered by Burroughs Wellcome, which conducted phase I and II clinical trials in more than 700 patients. Due to its potentially superior properties to those of methotrexate, it was expected that piritrexim would be active in certain methotrexate-resistant tumors. Tumor responses were noted in patients with advanced bladder cancer, Kaposi's sarcoma, colon cancer, melanoma, head and neck cancer and other cancer types. In published phase II studies, piritrexim demonstrated objective response rates ranging from 23 to 75% in patients with advanced bladder cancer who failed a standard first-line chemotherapy regimen. In March 1995, ILEX acquired an exclusive, worldwide license to patents held by Burroughs Wellcome covering the composition and use of piritrexim for all cancer indications. Under the terms of the agreement, ILEX paid a licensing fee and is obligated to pay Wellcome royalties on net sales of piritrexim. In December 1996, ILEX formed a joint venture with MPI Enterprises for the manufacture and marketing of piritrexim.