FOSTER CITY, CA -- March 3, 1999 -- Gilead Sciences, Inc. announced today results from preliminary analyses of two studies designed to evaluate a 60 mg once daily dose of Preveon(R) (adefovir dipivoxil) for the treatment of HIV-infected patients.
Results from recently unblinded studies indicate that treatment with 60 mg monotherapy provides statistically significant anti-HIV activity compared to placebo in treatment-naive patients and that combination regimens including 60 mg or 120 mg doses of Preveon have similar efficacy in treatment-experienced patients.
In addition, patients receiving the Preveon 60 mg dose showed a significant reduction in the incidence of nephrotoxicity compared to patients receiving Preveon 120 mg. Additional analyses of these data are ongoing and more complete results will be presented at the 12th international conference on Antiviral Research in Jerusalem, Israel, March 21-26, 1999.
In November 1998, the United States Food and Drug Administration granted Fast Track designation to Preveon for the treatment of HIV-infected patients. Gilead intends to file an NDA for the accelerated approval of Preveon for the treatment of HIV-infected patients with clinical, immunologic and/or virologic progression despite prior reverse transcriptase inhibitor therapy.
A four-week, randomised, double-blind, placebo-controlled trial was conducted at four U.S. centres. Forty-seven HIV-infected patients with HIV RNA greater than 5,000 copies/ml and a CD4 cell count greater than or equal to 150 cells/mm3 were enrolled. The primary objective of this study was to determine the anti-HIV activity of Preveon 60 mg monotherapy compared to placebo over four weeks in treatment-naive patients.
Results demonstrated that treatment with a 60 mg dose of Preveon monotherapy is associated with statistically significant anti-HIV activity compared to placebo. This activity was similar in magnitude to the anti-HIV activity of Preveon 120 mg monotherapy demonstrated in previous studies.
In another study, 214 patients were enrolled in a double-blind, dose-comparison trial, which was conducted at 22 centres in the U.S. Patients were required to have HIV RNA greater than 5,000 copies/ml and a CD4 cell count greater than or equal to 100 cells/mm3 upon enrolment into the trial. Patients had not previously received protease inhibitors, but had received extensive prior treatment with nucleoside reverse transcriptase inhibitors.
Patients in this study were randomly assigned to receive either Preveon 60 mg or 120 mg along with a combination of either nelfinavir and saquinavir or of a nucleoside reverse transcriptase inhibitor (AZT, 3TC or d4T) plus nelfinavir or saquinavir.
Twenty-week interim data demonstrate that triple drug regimens containing Preveon 60 mg were as effective as triple drug regimens containing 120 mg with regard to the proportion of patients whose HIV RNA was below the limit of quantification (less than or equal to 400 copies/ml) at week 20 (the primary endpoint of the study).
In addition, both doses of Preveon were equally effective in decreasing HIV RNA and increasing CD4 cell counts over the study period. Patients who received the 60 mg dose of Preveon also had a significant reduction in the incidence of nephrotoxicity compared to those who received the 120 mg dose.
Preveon is an investigational, once-daily, orally administered, reverse transcriptase inhibitor under development for the potential treatment of HIV. To date, more than 8,500 patients have been enrolled in clinical studies of Preveon, including more than 7,000 in the Expanded Access Program, at one of two dose levels (60 mg or 120 mg once daily). In all studies, Preveon is co-administered with L-carnitine, a nutritional supplement.
During clinical testing, the most common side effects reported with Preveon have been dose-related gastrointestinal effects, including nausea and loss of appetite. Nephrotoxicity, including changes in serum creatinine and phosphate, is the most important drug-related toxicity. These changes are generally gradual in onset, asymptomatic, detectable by routine monitoring and resolvable upon dose reduction or withdrawal. Some patients have experienced elevations in liver transaminases.
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