PR Newswire; Monday June 29, 8:27 am EST

The median plasma virus levels in all five treatment groups at 16 weeks had decreased to less than 400 copies. Six of 11 patients (55%) who received Ziagen along with the investigational protease inhibitor Agenerase(TM) (amprenavir), had undetectable levels of virus (less than 50 copies/mL of plasma)(A), while 6 of 10 patients (60%) receiving Ziagen + indinavir and 6 of 10 patients (60%) taking Ziagen + nelfinavir had undetectable levels of virus. In the treatment groups receiving Ziagen + ritonavir and Ziagen + saquinavir (sgc), 6 of 8 (75%) and 5 of 10 (50%) respectively had undetectable virus. Approximately 50-70 percent of patients across all treatment arms had virus levels beneath 50 copies. Differences between arms were not statistically significant.

"These results appear to support results from other studies which have suggested that regimens containing Ziagen are highly active against HIV," said Stephen LaFon, International Project Leader for Ziagen at Glaxo Wellcome. "More importantly, these results provide a further suggestion about the durability of effect that regimens containing Ziagen may have."

The study randomized 82 patients with HIV to one of five treatment groups: Ziagen + amprenavir, Ziagen + indinavir, Ziagen + nelfinavir, Ziagen + saquinavir (soft gel caps), and Ziagen + ritonavir. Patients admitted to the trial had not previously been treated with antiretroviral drugs, had CD4 cell counts above 100 and viral loads greater than 5,000 copies/mL of blood. Data were presented on the 55 patients who had reached 32 weeks; 49 of whom remained on randomized study medications during that time. Nineteen patients discontinued the study prematurely and were split fairly evenly between those lost to follow-up, those experiencing treatment limiting side effects, and those who met therapy switch criteria. Eight patients who were originally randomized in the study never initiated therapy.

Ziagen and Agenerase are in Phase III clinical development by Glaxo Wellcome as treatments for HIV and AIDS. Agenerase appears to be a highly active protease inhibitor, which is being studied with nucleoside analogues, other protease inhibitors and non-nucleosides. Both drugs are dosed twice daily and with no food or water restrictions or requirements.

"One of the encouraging observations in this study is that together with Ziagen, Agenerase looks to have similar antiviral activity as do the currently available protease inhibitors," said Mike Rogers, Ph.D., International Project Leader for Agenerase at Glaxo Wellcome.

"Data from this and other studies combining amprenavir with abacavir are encouraging," added Dr. Joshua Boger, Chairman, President and CEO of Vertex. "Results from numerous studies will complement a comprehensive data package now being compiled for amprenavir in preparation for regulatory submissions in the United States and Europe."

The study, presented today at the 12th World AIDS conference in Geneva, showed that each of the two-drug combinations studied were generally well- tolerated with the most commonly reported adverse events consisting of nausea, vomiting, diarrhea and headache. Serious adverse events observed by treatment arm include fever (Agenerase), skin rash (indinavir), diarrhea and drug reactions (nelfinavir), and diarrhea and drug reactions (ritonavir). There were no serious adverse events in the saquinavir arm. Four patients in the study discontinued treatment due to symptoms consistent with a hypersensitivity reaction that has been reported in some patients receiving Ziagen.

In clinical trials to date, Agenerase has been generally well-tolerated with the most commonly observed adverse events consisting of nausea, vomiting, headache and rash. In clinical trials, Ziagen has been generally well- tolerated with the most commonly reported adverse events consisting of headache, nausea, vomiting, malaise and rash. In three percent of patients receiving Ziagen, a hypersensitivity reaction has been observed which is characterized by fever with nausea and/or malaise and, possibly an accompanying skin rash. Symptoms of this reaction generally occur between several days to six weeks after initiating therapy and resolve following discontinuation of Ziagen. Patients experiencing this reaction must not take Ziagen again as restarting the drug after a hypersensitivity reaction has resulted in cases of a life-threatening and, in one instance, fatal reaction.

Agenerase was discovered by scientists at Vertex Pharmaceuticals, which licensed the compound to Glaxo Wellcome. Ziagen was discovered and is being developed by Glaxo Wellcome. The rights to related compounds and technology, including intermediates, used in the manufacture of Ziagen, resulting from research by Dr. Robert Vince, et al, were licensed to Glaxo Wellcome by the University of Minnesota.

Glaxo Wellcome is the pharmaceutical industry leader in HIV research and therapies. The company currently manufactures and markets Epivir(R) (lamivudine; 3TC) and Retrovir(R) (zidovudine; AZT), as well as Combivir(R) (lamivudine/zidovudine)(B) which combines Epivir and Retrovir into one tablet. Vertex Pharmaceuticals Incorporated is engaged in the discovery, development and commercialization of novel, small molecule pharmaceuticals for the treatment of diseases for which there are currently limited or no effective treatments. The Company is a leader in the use of structure-based drug design, an approach to drug discovery that integrates advanced biology, biophysics and chemistry. The Company is concentrating on the discovery and development of drugs for the treatment of viral diseases, multidrug resistance in cancer, autoimmune and inflammatory diseases, and neurodegenerative diseases.

There can be no assurance that clinical trials will continue, that initial clinical trial results will be predictive of any future results, that drugs under development by Vertex or its partners will receive marketing approval from the U.S. Food and Drug Administration or other regulatory authorities, or that drugs, if any, which receive such approval will be marketed successfully. Investors are also directed to consider other risks and uncertainties discussed in Vertex documents filed with the Securities and Exchange Commission. Vertex's press releases are also available by fax-on-demand at 800-758-5804 -- Code: 938395

NOTE(A): Viral load assays used in this study were the Roche Amplicor (less than 400 copies/mL of plasma) and the Roche Ultrasensitive assay (less than 50 copies/mL of plasma) which has yet to be validated. (B): Epivir is also known as 3TC(R)

SOURCE: Vertex Pharmaceuticals Incorporated

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