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VIRACEPT Exhibits Potency After 12 Months

Clinical investigators will present long-term virological and immunological results from Study 511, a key clinical trial that evaluated VIRACEPT taken in combination with Retrovir(R) (zidovudine or AZT) and Epivir(R) (lamivudine or 3TC) in 297 patients whose mean viral load (the amount of HIV in the blood) was 153,044 viral copies per mL of plasma. Their mean CD4+ T-cell count (infection-fighting cells of the immune system) was 288 cells/mm3. After 12 months of treatment, the mean reduction in viral load for those taking 750mg of VIRACEPT three times daily (TID) was greater than 99% (2.3 log10) using the Roche AMPLICOR(TM) HIV Monitor (a PCR-based assay with a lower limit of quantification of 400 copies/mL). Viral load was reduced below the limit of quantification of the Amplicor assay in the plasma of 81% of patients receiving 12 months of the VIRACEPT combination therapy. CD4+ T cells continued to show progressive improvement over the 12-month period with a mean increase from baseline of 180 cells/mm3, up from 146 cells/mm3 at six months.(1)

VIRACEPT is indicated for the treatment of HIV infection when antiretroviral therapy is warranted. This indication is based on analyses of surrogate marker changes in patients who received VIRACEPT in combination with nucleoside analogues or alone for up to 24 weeks. At present, there are no results from controlled trials evaluating the effect of therapy with VIRACEPT on clinical progression of HIV infection, such as survival or the incidence of opportunistic infections. The most commonly observed adverse event of moderate or greater severity in clinical trials of VIRACEPT was diarrhea, which was generally controlled with over-the-counter medications.

Combination of VIRACEPT and Saquinavir Soft Gel Formulation

Preliminary results will be reported from an open study of the combination of VIRACEPT and FORTOVASE(TM) (saquinavir soft gel formulation, SGC) in 14 patients, most of whom had been treated previously with other anti-retroviral drugs. The concomitant administration of standard doses of VIRACEPT increased patients' exposure to saquinavir SGC five-fold. Viral load fell below the limit of quantification (500 copies/mL) in 80% of ten patients who were treated for ten months with the standard dose of VIRACEPT plus 800mg of saquinavir SGC TID. Seven of these patients were also receiving one or more anti-retroviral drugs from the class of reverse transcriptase inhibitors. The HIV mutation uniquely associated with resistance to VIRACEPT was not detected in virus from any of 12 patients studied by genotypic analysis after five to seven months of treatment with the combination. The combination of VIRACEPT and saquinavir SGC was generally well tolerated in the study; the most commonly observed adverse event of moderate or greater intensity was diarrhea.(2)

Some VIRACEPT Patients Respond to Other Protease Inhibitors

Preliminary results will be presented from a study of patients who switched to treatment regimens containing other protease inhibitors after failing VIRACEPT therapy. Clinical investigators studied 12 patients who, after virologic failure during VIRACEPT clinical trials, switched to the combination of 400mg ritonavir twice daily (BID) + Invirase(R) (saquinavir) (400mg BID) + d4T (40mg BID) + 3TC (150mg BID). At baseline, the mean viral load in these patients was 130,646 copies/mL; mean CD4+ T cell count was 208. Viral load fell below the limit of quantification (500 copies/mL) in all 12 patients who received the new protease inhibitor-containing therapy. Viral load has remained below the limit of quantification in six of seven patients who have received the new therapy for 16 weeks. Viral load has remained below the limit of quantification in four of the remaining five patients who have received the new protease inhibitor-containing therapy for periods less than 16 weeks. Investigator Keith Henry, M.D. said, ``These preliminary results suggest that patients who experience virologic failure while taking VIRACEPT are not necessarily precluded from responding to treatment regimens containing other protease inhibitors.'' Dr. Henry will also report that viral load fell below 500 copies/mL in three of seven patients in a second group of extensively pre-treated patients (all of those tested were resistant to 3TC) from another VIRACEPT clinical trial who were switched to the regimen containing ritonavir, saquinavir, d4T and 3TC. At baseline, the mean viral load in these seven patients was 263,027; mean CD4+ T cell count was 65.(3)

Expanded Data on VIRACEPT Safety

Additional safety data has been collected from patients enrolled in the VIRACEPT Expanded Access Program, which was initiated in the United States in September 1996 and continued until VIRACEPT was cleared for marketing in March 1997. The program was designed to obtain additional safety information on VIRACEPT in patients who were unable to take commercially available protease inhibitors due to intolerance, contraindication, or failure, and who had CD4+ T-cell counts less than or equal to 50. These criteria were revised in January 1997 to include people with CD4+ T-cell counts less than or equal to 100 who were unable to take indinavir and/or ritonavir due to intolerance or prior failure. 3125 people were enrolled in the program, and 2197 people were evaluated for safety. This population included a diverse array of patients: 12% of participants were African-American; 11% were Latino; and 8% were women. The most frequently reported side effect of moderate or greater intensity in patients evaluated for safety was diarrhea (7%). Only 6% of people evaluated for safety discontinued use of the drug due to any adverse event. Overall, VIRACEPT was generally well tolerated in this heavily pretreated patient population with advanced HIV disease.(4)

About VIRACEPT

VIRACEPT was cleared for marketing in March 1997. Currently, more than 50,000 people in the U.S. are estimated to be taking VIRACEPT. VIRACEPT has been evaluated in more than 5000 people around the world. VIRACEPT was the first HIV protease inhibitor in the U.S. to receive simultaneous marketing clearance for use in adults and children. VIRACEPT was approved in Switzerland in June 1997; approval is pending in Canada as well as in the European Union (15 countries) and five non-European countries, including Japan.

Recently a key committee of the National Institutes of Health issued new HIV treatment guidelines(5) that strongly urge a general policy of earlier intervention in the disease with three-drug combination therapy containing a potent protease inhibitor like VIRACEPT. This recommendation was repeated by the New England Journal of Medicine in a recent editorial.(6)

Currently, the VIRACEPT Expanded Access Program is being conducted in Canada, with more than 300 people enrolled to date. An additional Expanded Access Program is being conducted in Europe, with more than 1900 people currently enrolled. Agouron provides VIRACEPT without charge to any child in the United States who is not covered by public or private health insurance. For product information, patients, physicians and care givers may call Agouron Customer Communications toll free at 1-888-847-2237. For information on the VIRACEPT Assistance Program for both adults and children, call toll free 1-888-777-6637.

VIRACEPT has been developed by Agouron in collaboration with the pharmaceutical division of Japan Tobacco Inc. VIRACEPT is being marketed in the U.S. by Agouron.

Agouron Pharmaceuticals, Inc. is an integrated pharmaceutical company committed to discovery, development, manufacturing, and marketing of small-molecule drugs engineered to inactivate proteins which play key roles in cancer, AIDS, and other serious diseases.

Full prescribing information for VIRACEPT follows.

VIRACEPT(R) is a registered trademark of Agouron Pharmaceuticals, Inc.

AMPLICOR(TM) is a trademark of Roche Laboratories, Inc.

INVIRASE(R) is a registered trademark of Roche Laboratories, Inc.

FORTOVASE(TM) is a trademark of Roche Laboratories, Inc.

Retrovir(R) and Epivir(R) are registered trademarks of Glaxo Wellcome Oncology/HIV.

Zerit(R) is a registered trademark of Bristol-Myers Squibb Oncology.

For further information about Agouron Pharmaceuticals, Inc., please see Agouron's web site at: http://www.agouron.com

AGOURON PHARMACEUTICALS, INC. La Jolla, CA 92037, USA

(1) 37th Interscience Conference on Antimicrobial Agents and Chemotherapy meeting, poster 1-101, September 28-October 1, 1997

(2) 37th Interscience Conference on Antimicrobial Agents and Chemotherapy meeting, poster 1-191, September 28-October 1, 1997

(3) 37th Interscience Conference on Antimicrobial Agents and Chemotherapy meeting, poster 1-204, September 28-October 1, 1997

(4) 37th Interscience Conference on Antimicrobial Agents and Chemotherapy meeting, poster 1-102, September 28-October 1, 1997

(5) Report of the NIH Panel to Define Principles of Therapy of HIV Infection. 1997. Figure 5.

(6) New England Journal of Medicine, September 11, 1997

Copyright (c) 1997/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
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Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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