UPJOHN’s BHAP-E REVERSE TRANSCRIPTASE INHIBITOR IS SLATED TO ENTER PHASE I
UPJOHN's BHAP-E REVERSE TRANSCRIPTASE INHIBITOR IS SLATED TO ENTER PHASE I in September as a monotherapy treatment for AIDS, the company announced at the HIV Drug Resistance Meeting preceding the VIII International Conference on AIDS in Amsterdam July 22. Upjohn said that the reverse transcriptase inhibitor "is considerably more potent in blocking growth of the HIV virus in human cells than the currently approved drugs AZT [Burroughs Wellcome's Retrovir] and ddI [Bristol-Myers Squibb's Videx]." The company said it will file an IND shortly. In vitro data suggest that BHAP-E may be able to overcome resistance problems encountered in early testing of other non- nucleoside reverse transcriptase inhibitors, Upjohn said. The company explained that studies performed at the University of California at Los Angeles Medical School and the University of Nebraska Medical Center show that RT enzymes demonstrating resistance to other inhibitors "remain susceptible to inhibition by low concentrations of the potent BHAP-E." These data "indicate that cross-resistance among non-nucleoside RT inhibitors varies between compounds." Therefore Upjohn believes there is a possibility that BHAP-E may be effective against drug resistant strains of HIV. Companies including Merck and Boehringer Ingelheim have found the emergence of resistant strains of HIV to be a stumbling block in the development of their reverse transcriptase inhibitors and are now investigating the use of the compounds in combination therapy with nucleosides such as AZT and ddI. In December, Janssen reported that it had not encountered a resistance problem with its TIBO-derived RT inhibitors, which at that time were in clinicals in Europe ("The Pink Sheet" Dec. 2, 1991, T&G-7). Upjohn said it may study BHAP-E in combination with AZT if warranted. BHAP-E is an analog of another Upjohn drug, U-87,201E. That compound currently is in Phase II trials for the treatment of AIDS.
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