LA JOLLA, Calif., Feb. 3 /PRNewswire/ -- Agouron Pharmaceuticals, Inc.
(Nasdaq: AGPH) today summarized promising results from clinical trials of
VIRACEPT(R) (nelfinavir mesylate) used in combination with other protease
inhibitors and other anti-HIV drugs. These results, which are being presented
this week at the 5th Conference on Retroviruses and Opportunistic Infections
in Chicago, suggest additional treatment options for people taking or
considering VIRACEPT in combination with other anti-HIV drugs.
VIRACEPT and Fortovase(TM)
VIRACEPT was evaluated in combination with Fortovase(TM) (saquinavir soft
gel) in 14 patients in a three times daily (TID) dosing regimen that has
been ongoing for more than one year. The patients' mean baseline viral load
and CD4+ T-cell counts were 39,917 viral copies/mL of plasma and 327
cells/mm3, respectively. After 12 months of treatment, the median CD4+ T-cell
count increase was 101 cells and approximately 80% (7/9) of patients had HIV
RNA below the limit of detection (<500 copies/mL), with a median viral load
reduction of 2.38 log10. Genotypic analyses conducted throughout the study
found no occurrence of the mutation D30N (the mutation commonly associated
with VIRACEPT). Four patients had the mutations G48V or L90M (the mutations
commonly associated with resistance to saquinavir).
VIRACEPT and Norvir(TM)
VIRACEPT was well tolerated in combination with Norvir(TM) (ritonavir) in
20 patients receiving twice daily (BID) dosing. The patients' mean viral load
at baseline was 32,459 viral copies/ml of plasma. Their mean CD4+ T-cell
count at baseline was 325 cells/mm3. All patients received 400mg of ritonavir
q12h (every 12 hours) with VIRACEPT administered either at 500mg q12h or 750mg
q12h. After 12 weeks of therapy, 17 of 19 patients have viral loads below the
limit of detection (using the Roche AMPLICOR(TM) HIV assay with a lower limit
of detection of 400 copies/mL). Reverse transcriptase inhibitors have been
added to the VIRACEPT and Norvir treatment regimens. The most commonly
reported side effect for this combination was diarrhea.
VIRACEPT and Crixivan(R)
The combination of VIRACEPT and Crixivan(R) (indinavir) was evaluated in
21 patients who received twice daily (BID) dosing of 750mg VIRACEPT and 1000mg
Crixivan. HIV in plasma fell below the limit of detection by the Roche
AMPLICOR assay (<200 copies/mL) in 10 patients receiving this combination for
periods between 12 and 32 weeks and, in 6 of these patients, below the limit
of detection by an ultrasensitive assay (<50 copies/mL). The mean increase in
CD4+ T-cells (infection-fighting cells of the immune system) in the 21
patients after treatment for periods between 12 and 32 weeks was 133
cells/mm3. The most commonly reported side effect for this combination was
diarrhea. Currently under evaluation is the twice daily regimen of 1000mg
Crixivan plus 1000mg VIRACEPT. A further escalation to 1250mg VIRACEPT BID in
the combination is planned.
VIRACEPT and Non-Nucleoside Reverse Transcriptase Inhibitors
Results from combination studies of VIRACEPT with non-nucleoside reverse
transcriptase inhibitors (NNRTIs) also were presented at the conference.
Gail Skowron, M.D., Brown University, presented pharmacokinetic and clinical
data from a study of 25 patients who were given VIRACEPT in combination with
Viramune(R) (nevirapine) + Zerit(R) (d4T or stavudine). Pharmacokinetic
studies demonstrated that neither nevirapine nor VIRACEPT altered the plasma
concentration of the other, indicating that no adjustments in dosage of either
drug is needed in the combination. Five patients discontinued therapy due to
adverse events (rash, elevated lipase, and hepatitis/rash). Eight of nine
patients who completed 21 weeks of therapy have experienced reductions in
viral load below the limit of detection (<400 copies/mL).
VIRACEPT was also studied with Sustiva(TM) (efavirenz or DMP266), a NNRTI
in development. Pharmacokinetic evaluation showed a 15% increase in VIRACEPT
exposure, resulting in no requirement for dosing modification. Efficacy
studies are underway to further evaluate this treatment regimen.
VIRACEPT and Glaxo Wellcome 1592
VIRACEPT was evaluated in combination with abacavir (Glaxo Wellcome 1592),
another antiretroviral drug in development. This combination was found to be
safe and well tolerated after 16 weeks of treatment. Seven of nine patients
on this combination achieved viral load suppression below the limit of
detection at 16 weeks (<400 copies/mL). The median CD4 increase from baseline
was approximately 130 cells.
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 http://www.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.
Norvir(TM) is a trademark of Abbott Laboratories.
AMPLICOR(TM) is a trademark of Roche Laboratories, Inc.
Fortovase(TM) is a trademark of Roche Laboratories, Inc.
Viramune(R) is a registered trademark of Roxane Laboratories, Inc.
Zerit(R) is a registered trademark of Bristol-Myers Squibb Company.
Sustiva(TM) is a trademark of DuPont Merck Pharmaceuticals, Inc.
SOURCE Agouron Pharmaceuticals, Inc.
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Related links:
http://www.agouron.com
CONTACT:
Investors: Donna Nichols, Vice President,
Head of Corporate Communications, 619-622-3009, or Media: Joy
Schmitt, Manager, Product Public Relations, 619-622-3220, both of
Agouron Pharmaceuticals, Inc.
CNOC: http://www.prnewswire.com or fax, 800-758-5804, ext.
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