AEGiS-GMHC: Treatment Briefs: Some Competition for 1592

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Treatment Briefs: Some Competition for 1592

Treatment Issues, Vol 11, No 4/5; April 1997
David Gilden

**DMP 266: DMP 266 is Du Pont Merck's experimental nonnucleoside reverse transcriptase inhibitor. In an initial, trial of low-dose DMP 266 (200 mg once a day) plus indinavir, viral loads were 2.5 logs (99.7%) below baseline at 42 weeks, with 80% of the 21 participants below the viral load assay's level of detection (400 HIV RNA copies/ml of plasma). There are a number of DMP 266 trials in progress or about to begin, including several looking at the drug as part of second-line, replacement regimes in people with long experience on other drugs.

In April meetings with the community, Du Pont Merck discussed its tentative plans for expanded access. The company, like Glaxo, is arguing that drug supplies are limited. It is considering initiating a small compassionate use program in the next few months with a larger, but still modest expanded access program to commence next January. The company would like to organize a joint program that would include Glaxo's 1592 or other drugs, so as to create a fresh multidrug combination that would have a reasonable chance of success in people failing on the drugs available at present.

**PMPA: Gilead Sciences announced May 7 that it was commencing a small five-week Phase I/II human trial of an oral prodrug form of PMPA (known as bis-POC-PMPA). The placebo-controlled study will evaluate different doses of oral PMPA in volunteers with CD4 counts above 200 and viral loads over 10,000.

PMPA is a nucleoside analog that has been partly activated through the addition of a phosphate group. In an initial human test, intravenous PMPA monotherapy at 3 mg/kg of body weight reduced HIV levels by more than 1.1 log (92%) after a mere eight injections (on day one and days eight through 14). This reduction was sustained for a week after treatment was terminated. The oral form may be more active than the intravenous form because it better penetrates cells, where it is converted to regular PMPA.

**d4T/ddI: The final results of a year-long pilot study of this combination in treatment-naive volunteers were released in April. The average viral load reduction after a year was about 1.3 logs (95%), which is noteworthy but somewhat less than earlier interim analyses indicated. Average CD4 count increased from 330 to 450. Participants in the three higher dose trial arms appeared to receive greater benefit than those in the two lower dose arms.

Peripheral neuropathy has been a major concern with this combination since both ddI and d4T can have this effect when used individually. Only two of the 86 trial volunteers suffered serious peripheral neuropathy, but this cohort was a relatively healthy one and only 20% received full dose of both drugs.

Bristol-Myers Squibb, the drugs' manufacturer, is moving on to trials of d4T/ddI/indinavir. Also, it is working on a once daily adult dose schedule for ddI and is creating a specially coated time-release ddI capsule. That capsule would replace the awkward chewable buffer- containing tablets, which must be taken between meals and frequently cause stomach upset. Bristol expects to seek FDA approval of the capsule early next year.

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Copyright © 1997 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011 fredg@gmhc.org http://www.gmhc.org

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