PR Newswire; Monday June 29, 7:30 am EST

A secondary analysis of those patients in the arm containing Ziagen who actually received study drug for 16 weeks showed that 86 percent (62 of 72) had undetectable levels of virus in the plasma. Four patients originally randomized to the arm containing Ziagen never began treatment, and 11 patients discontinued the trial early due to adverse events or were lost to follow up.

Perhaps of greater significance are data suggesting that 54 percent of all patients assigned to the treatment arm containing Ziagen, and 67 percent of patients who actually received study drug for 16 weeks, had less than 50 viral copies/mL of plasma. Results of this study were reported today at the 12th World AIDS Conference in Geneva.

"These results, while preliminary, are impressive with regard to the high percentage of patients who had marked reductions in HIV, and the speed with which these reductions in virus occurred," said Margaret Fischl, M.D., lead investigator for the study from the University of Miami. "This appears to be a very potent regimen in this patient population and can also be dosed very simply."

Ziagen is dosed as one 300 mg tablet twice daily with no food or water restrictions or requirements. Ziagen is not associated with any drug interactions with other antiretroviral drugs. The combination of Ziagen+Epivir+Retrovir -- with Epivir+Retrovir being dosed as the combination tablet Combivir(R) (lamivudine/zidovudine) -- can be dosed with two pills in the morning and two pills at night.

Ziagen, like Epivir and Retrovir, belongs to a class of drugs known as nucleoside analogue reverse transcriptase inhibitors. Data from 16-week surrogate endpoint studies have suggested that in some previously untreated patients, regimens containing Ziagen have a level of antiviral activity often associated with those containing a protease inhibitor and two nucleosides, though direct comparisons are not complete.

The study reported today compared the antiviral activity, safety and tolerance of Ziagen+Epivir+Retrovir versus Epivir+Retrovir. The study enrolled 173 patients who were randomized to one of these two regimens (87 to Ziagen+Epivir+Retrovir; 86 to Epivir+Retrovir). Patients enrolled had no previous history of antiretroviral drug treatment and had CD4 cell counts greater than 100 cells/mm3. The study is designed to last 48 weeks, however all patients were allowed to switch treatments after 16 weeks to Ziagen+Epivir+Retrovir. Results presented today are the planned evaluation after 16 weeks of the study.

In the control group, 35 percent of the 86 patients originally randomized to receive Epivir+Retrovir had undetectable levels of virus, with 43 percent of those who actually received study drug for 16 weeks on this arm having undetectable virus. Fifteen percent of the original patients in this group -- as well as 19 percent who actually received study drug for 16 weeks -- had less than 50 viral copies/mL of blood.

Treatment was generally well tolerated in this study with the most commonly reported side effects consisting of nausea, malaise and fatigue, headache, vomiting, diarrhea and loss of appetite. There were no significant differences in the side effects in the two treatment arms. Also, two patients (2%) experienced a hypersensitivity reaction consisting of fever with nausea and/or malaise and, possibly, an accompanying rash. Symptoms of this reaction generally occur from 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.

"The preliminary results from this study appear to support the antiviral potency and tolerability that have been seen in smaller phase II studies," said Steve LaFon, international project leader for Ziagen at Glaxo Wellcome. "A regimen such as this which is highly potent against HIV and contains drugs from only one class may represent an important treatment strategy for some previously untreated patients in the future."

Ziagen is currently available through an expanded access program to patients who are no longer maintaining viral suppression with their current treatments. To date, approximately 5,000 patients have enrolled in either this program or an earlier open label access program. Physicians interested in enrolling patients into the Ziagen expanded access program can receive information by calling 1-800-501-4672.

Ziagen was discovered and is being developed by Glaxo Wellcome (NYSE: GLX - news). 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 in 1992. Glaxo Wellcome Inc. is the pharmaceutical industry leader in HIV research and therapies. The company currently manufactures and markets Epivir and Retrovir, as well as Combivir (lamivudine/zidovudine) which combines Epivir and Retrovir into one tablet.

Note a - Viral load assays used in this study included the Roche Amplicor (less than 400 copies/mL of plasma) and the Roche Ultrasensitive (less than 50 copies) which has yet to be validated.

Note b - Epivir is also known as 3TC(R).

SOURCE: Glaxo Wellcome Inc.

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