PRNewswire - Monday, November 9, 1998

In an ongoing European study conducted at 34 sites that will continue to 96 weeks, 283 patients were initially randomized to receive either the standard three times daily (TID) dose of 750mg VIRACEPT or one of three twice daily (BID) VIRACEPT doses (1250mg, 1000mg, or 750mg) in combination with standard doses of Zerit(R) (d4T or stavudine) and Epivir(R) (3TC or lamivudine). The study protocol was subsequently amended to consolidate the comparison to the 1250mg BID vs. 750mg TID VIRACEPT regimens; patients originally randomized to one of the lower doses were switched to 1250mg BID.

Preliminary results from the BID dosing group were compared with results from the TID dosing group. In an on-treatment analysis of patients who have reached the 48 week time point, HIV RNA in plasma fell below the limit of quantification by the Roche Amplicor(TM) HIV-1 Monitor Test (<400 HIV RNA copies/mL) in approximately 80% of patients in both the BID dosing group (133/168) and the TID dosing group (48/59). Sixty-eight percent of patients (112/166) in the BID dosing group and 64% of patients (38/59) in the TID dosing group achieved HIV RNA levels below the limit of quantification by an ultrasensitive assay (<50 copies/mL) at 48 weeks.

A very conservative intent-to-treat analysis, where patients who discontinue for any reason are counted as drug failures, (noncompleter = failure), was also conducted. At 16 weeks, a point at which data have shown early signs of the inferiority of BID to TID dosing for other products, the response rate in the VIRACEPT BID group was higher than for the TID group by this analysis: 80% of patients in the BID group and 76% of patients in the TID group had HIV RNA levels below 400 copies/mL. At 48 weeks, 66% of patients in both groups had HIV RNA levels below 400 copies/mL by this intent-to-treat analysis.

Mean CD4+ T-cell counts (infectious-fighting cells of the immune system) at 48 weeks increased by 195 cells/mm3 and 174 cells/mm3 in the BID group and the TID group, respectively. Prior to treatment, the mean amount of HIV RNA in plasma of patients was approximately 5.0 log10 viral copies/mL of plasma. The mean baseline CD4+ T-cell counts were 273 and 254 cells/mm3 in the BID and TID groups, respectively. Patients enrolled in this study had less than six months of prior nucleoside anti-retroviral therapy.

"The fundamental pharmacokinetic profile of a protease inhibitor should be expected to predict the feasibility of effective BID dosing," explains Dr. Brad Kerr, Head of Clinical Pharmacology, Agouron Pharmaceuticals, Inc. ("Agouron"). "The half-life and stable drug levels of nelfinavir support the use of BID dosing."

"The recent decision by Merck to halt BID trials of their protease inhibitor Crixivan(R) based on preliminary 16-24 week results has not altered our intention of pursuing this important dosing improvement for VIRACEPT," said Dr. Barry Quart, Senior Vice President and Head of Drug Development, Agouron. "Based on the encouraging results emerging from this much larger data set with patients treated out to one year and beyond, Agouron reasserts its intention to seek approval for a BID dosing indication from health authorities."

A retrospective analysis of patients in this study revealed a low incidence (<2%) of clinical features of lipodystrophy (5/283) with late onset detected between weeks 40 and 72. Excellent reduction in viral load was observed for patients that developed lipodystrophy, warranting further evaluation of the possible association between viral load suppression and lipodystrophy.

The only side effect of moderate or greater intensity to occur in more than 5% of patients receiving VIRACEPT was diarrhea, which occurred at a rate of 15% in the combined arms of the study. New onset or exacerbation of diabetes mellitus and hyperglycemia, redistribution or accumulation of body fat, as well as increased bleeding in patients with hemophilia types A and B, have been reported with protease inhibitors.

VIRACEPT is indicated in combination with anti-retroviral nucleoside analogues for the treatment of HIV-1 infected patients. The combination of VIRACEPT with other anti-retroviral agents reduces viral load in plasma and increases CD4 cell counts.

For More Information Contact: 011-44-162-882-1600

VIRACEPT(TM) is a trademark of Agouron Pharmaceuticals, Inc. and is marketed outside of the U.S. and Canada by F. Hoffmann-La Roche Ltd. Zerit(R) is a registered trademark of Bristol-Myers Squibb Company. Crixivan(R) is a registered trademark of Merck & Co. Epivir(R) is a registered trademark of Glaxo Wellcome Oncology/HIV. AMPLICOR(TM) is a trademark of Roche Laboratories, Inc.

SOURCE Agouron Pharmaceuticals Web Site: http://www.agouron.com
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