LA JOLLA, Calif., Jan. 23 /PRNewswire/ -- Agouron Pharmaceuticals, Inc.
(Nasdaq-NNM: AGPH) today summarized results from clinical trials of the
company's HIV protease inhibitor VIRACEPT(R) (nelfinavir mesylate).  Included
are results from pivotal phase II/III clinical trials which form the basis of
a New Drug Application submitted by Agouron to the U.S. Food and Drug
Administration last month and which represent significant new evidence of the
safety and efficacy of VIRACEPT.

    General Safety and Efficacy
    Each of three double-blind clinical trials evaluated two doses of
VIRACEPT: 500mg or 750mg VIRACEPT taken three times daily with meals.  In one
study, 91 HIV-positive patients were randomized to receive either of the two
doses of VIRACEPT alone.  In a second study, 297 patients were randomized to
receive one of the two VIRACEPT doses plus stavudine (d4T), or d4T alone.  In
a third study, 308 patients were randomized to receive one of the two VIRACEPT
doses plus zidovudine (AZT) and lamivudine (3TC), or AZT and 3TC alone.
Primary endpoints followed in these trials were changes in two surrogate
markers: viral load (the amount of HIV detected in patients' blood) and CD4+
T cells (cells indicating the status of the immune system).  Viral load was
generally measured by a standard assay with a lower limit of detection of
500 HIV particles per ml.
    In all three trials, the treatment arms containing VIRACEPT produced
improvements in viral load compared with control arms that were highly
statistically significant (p<0.0001).  The treatment arms also produced
improvements in CD4+ T cell counts that were statistically significant in all
three trials.  When all patients were evaluated, the 500mg and 750mg doses of
VIRACEPT taken in combination with other anti-HIV drugs were equally
effective.
    VIRACEPT was safe and well tolerated in the pivotal trials.  The only side
effect of moderate (Grade 2) or greater intensity with a frequency of 10% or
greater was diarrhea.  Many of the side effects observed with other HIV
protease inhibitors were seen only rarely or not at all with VIRACEPT.  In the
three pivotal trials, 4% of 696 patients discontinued due to adverse events;
only 1.6% of patients discontinued due to diarrhea.  Despite the large number
of concurrent medications used by the 696 patients in the pivotal studies,
only one possible significant drug interaction was reported.  Very few
laboratory abnormalities were seen in patients on the studies.

    Triple Drug Therapy
    Dr. William Powderly, M.D. of Washington University School of Medicine,
St. Louis, will report results tomorrow from the clinical trial of primary
relevance to the prospective clinical use of VIRACEPT  --  the study of
VIRACEPT taken in combination with AZT and 3TC.  After six months of treatment
in this study, mean reductions in viral load (when measured to a lower limit
of 100 particles/ml) were 2.3 and 2.5 log10 (greater than 99%) for the triple
combination arms containing the 500mg and 750mg doses of VIRACEPT, and
1.4 log10 for AZT and 3TC alone.  Mean increases in CD4+ T cells were 160 and
155 cells for the triple combination arms containing VIRACEPT and 105 cells
for AZT and 3TC alone.
    At the end of six months, HIV levels fell below 500 particles per ml in
65% and 81%, of patients receiving the 500mg and 750mg three times daily doses
of VIRACEPT in triple drug therapy and in 18% of those receiving AZT and 3TC
alone.  In the triple drug therapy, the 500mg and 750mg doses of VIRACEPT were
equally effective in reducing HIV below 500 particles per ml in patients who
had baseline viral loads less than 100,000; but the 750mg dose was
significantly superior (p=0.01) in producing such reductions in patients with
baseline viral loads greater than 100,000.
    All VIRACEPT-containing treatment arms in the three clinical studies
produced acute reductions in viral load greater than 1.0 log10 (90%).
However, reductions were better sustained after four to six months by the
three drug combination than by the combination of VIRACEPT plus d4T (mean
reduction of 1.0 - 1.1 log10) or by VIRACEPT monotherapy (mean reduction of
0.2 - 0.6 log10).

    Resistance and Cross Resistance
    Genetic analysis of HIV from 55 patients from earlier pilot clinical
studies showed that resistance to VIRACEPT was strongly associated with a
specific mutation (D30N) in the HIV protease.  HIV which became resistant to
VIRACEPT due to the D30N mutation, whether isolated from patients or created
by genetic engineering techniques, remained susceptible to other HIV protease
inhibitors.  In a separate analysis, 14 of 23 (61%) clinical isolates from
patients who were reported to have failed therapy with indinavir, ritonavir or
saquinavir remained susceptible to nelfinavir.

    VIRACEPT Plus Other Protease Inhibitors
    Preliminary data indicate that the combination of VIRACEPT and a second
HIV protease inhibitor, Roche's Invirase(TM) soft gel (saquinavir), may be a
useful therapy.  In a pharmacokinetic study, co-administration of Invirase and
VIRACEPT resulted in significant increases in plasma levels of saquinavir and
no significant change in plasma levels of VIRACEPT.  After 12 weeks of
treatment with VIRACEPT and saquinavir, the median decrease in viral load of
13 patients was 2.0 log10 (99%) with HIV falling below 500 particles/ml in
eight patients.  The median increase in CD4+ T cells was 118 cells.  The
combination of VIRACEPT and saquinavir was generally safe and well tolerated.
An expanded trial of the combination VIRACEPT and saquinavir is currently in
progress.
    Additional pharmacokinetic studies of VIRACEPT taken concurrently with
other protease inhibitors showed that VIRACEPT increased trough plasma levels
of indinavir and that indinavir and ritonavir significantly increased plasma
levels of VIRACEPT.  Clinical trials to evaluate the safety and efficacy of
VIRACEPT in combination with these HIV protease inhibitors are planned.

   VIRACEPT Pediatric Study
    Data from a phase I study of children ages 2-13 indicate that VIRACEPT
oral powder and tablets yielded similar plasma concentrations.  A dose of 20-
25 mg/kg three times daily in children yielded steady-state plasma
concentrations similar to adult patients receiving 500mg or 750mg VIRACEPT
three times daily as tablets.  VIRACEPT was safe and well tolerated in
children.

    The results from VIRACEPT studies are the subjects of reports by several
investigators this week at the 4th Conference on Retroviruses and
Opportunistic Infections in Washington, D.C.  Presenters include: Dr. Keith
Henry, St. Paul Ramsey Medical Center in St. Paul; Dr. Steven Kravcik, Ottawa
General Hospital in Ottawa, Ontario; Dr. Paul Krogstad, University of
California, Los Angeles; and Dr. Amy Patick and Dr. Brad Kerr, Agouron
Pharmaceuticals, Inc.  VIRACEPT is being developed by Agouron in collaboration
with the pharmaceutical division of Japan Tobacco Inc.
    Agouron Pharmaceuticals, Inc. is a pioneer and leader in technologies
permitting the rational design of novel, small molecule drugs based upon the
molecular structures of proteins which play key roles in human disease.
Agouron is currently applying these technologies to the design and development
of novel drugs for treatment of cancer, AIDS, and other serious diseases.

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