VIRACEPT(R) Produces Durable Anti-HIV Effects For Two Years
February 3, 1998 08:31 AM
LA JOLLA, Calif., Feb. 3 /PRNewswire/ -- Agouron Pharmaceuticals, Inc. AGPH today announced preliminary results from an ongoing study in which HIV has remained below quantifiable levels in all patients taking VIRACEPT(R) (nelfinavir mesylate) combination therapy for 24 months. These results were presented at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago.
Twelve patients in the clinical study carried out at the Aaron Diamond AIDS Research Center received 750mg VIRACEPT TID (three times daily) + 200mg Retrovir(R) (AZT or zidovudine) TID and 150mg Epivir(R) (3TC or lamivudine) BID (twice daily). Prior to treatment, the patients' mean viral load (the amount of HIV in plasma) was 5.32 log10 and their mean baseline CD4+ T-cell count was 258 cells/mm3. One patient was switched to Crixivan(R) (indinavir) + Zerit(R) (d4T or stavudine) + 3TC after four weeks due to intolerance. After 12 weeks of treatment, all patients had HIV RNA levels below the level of quantification (<500 HIV RNA copies/mL with a branch DNA based assay). Three patients experienced virologic failure (two consecutive HIV RNA bDNA assays above the limit of detection) after 7, 15, and 17 months of VIRACEPT combination therapy, respectively, and were switched to d4T + Videx(R) (ddI or didanosine) + Norvir(TM) (ritonavir) + Invirase(R) (saquinavir), with one patient adding Rescriptor(R) (delaviridine) to the combination.
After 24 months of treatment, 11 of the 12 patients in the study had viral loads below the level of quantification using the bDNA assay (<500 HIV RNA copies/mL). One patient experienced acute hepatitis B infection while on this regimen which resulted in drug discontinuation and subsequent viral rebound at month 22. All eight patients who have maintained their VIRACEPT treatment for two years remain below the limit of detection (<500 HIV RNA copies/mL); HIV was consistently suppressed below 25 RNA copies/mL (ultrasensitive RT PCR assay) in four of those patients.
"The patients who switched to other drug regimens after VIRACEPT failure were susceptible to treatment with other HIV protease inhibitors used in combination with other anti-HIV drugs," said study principal investigator Martin Markowitz, M.D., of the Aaron Diamond AIDS Research Center in New York. "These results suggest that in the event of treatment failure, carefully managed patients may preserve their treatment options over time. The study also suggests the importance of switching treatments early after drug intolerance or demonstrated virologic failure to maintain treatment options for patients."
Genotypic testing conducted on virus isolated from the three patients who failed VIRACEPT-containing regimens revealed the following mutations: M184V (commonly associated with 3TC resistance) in all three patients; D30N (commonly associated with VIRACEPT resistance) in two; and L90M in one. No mutations associated with resistance were detected in patients who continued to respond to therapy, despite transient low level increases in HIV RNA as measured by the ultrasensitive RT PCR assay.
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. New onset or exacerbation of diabetes mellitus and hyperglycemia, as well as increased bleeding in patients with hemophilia types A and B, have been reported with protease inhibitors.
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 analogs 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.
Agouron Pharmaceuticals, Inc. is an integrated pharmaceutical company committed to discovery, development, manufacturing, and marketing of small molecule drugs engineered to inactivate proteins that play key roles in cancer, AIDS, and other serious diseases.
For further information about Agouron Pharmaceuticals, Inc., or about VIRACEPT, please see Agouron's website at agouron.com or dial toll free 1-888-VIRACEPT (847-2237). To receive full prescribing information for VIRACEPT via fax, dial 1-888-288-9639.
WIRES: Full prescribing information for VIRACEPT to follow.
VIRACEPT(R) is a registered trademark of Agouron Pharmaceuticals, Inc.
Retrovir(R) and Epivir(R) are registered trademarks of Glaxo Wellcome Oncology/HIV.
Crixivan(R) is a registered trademark of Merck & Co., Inc. Zerit(R) is a registered trademark of Bristol-Myers Squibb Company. Videx(R) is a registered trademark of the Bristol-Myers Squibb Company. Norvir(TM) is a trademark of Abbott Laboratories. Invirase(R) is a registered trademark of Roche Laboratories Inc. Rescriptor(R) is a registered trademark of the Pharmacia & UpJohn Company.
SOURCE Agouron Pharmaceuticals, Inc.
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