LA JOLLA, Calif., Feb. 3 /PRNewswire/ -- Agouron Pharmaceuticals, Inc.
(Nasdaq: AGPH) reported today that preliminary results from several clinical
studies indicate that twice daily dosing of its HIV protease inhibitor
VIRACEPT(R) (nelfinavir mesylate) produces anti-HIV effects comparable to
those resulting from standard three times daily dosing of the drug in
combination therapy. Results from clinical studies carried out in the U.S.
and in Europe are the subject of reports made at the 5th Conference on
Retroviruses and Opportunistic Infections in Chicago.
In an ongoing European study conducted at 24 sites, approximately 280
patients were randomized to receive either the standard dose of 750mg VIRACEPT
three times daily (TID) or one of three twice daily (BID) VIRACEPT regimens:
1250mg, 1000mg, or 750mg in combination with standard doses of Zerit(R) (d4T
or stavudine) and Epivir(R) (3TC or lamivudine). Preliminary results from the
TID dosing group were compared with results from the combined BID dosing
groups (the study has not yet been unblinded). HIV in plasma initially fell
below the limit of detection by the Roche AMPLICOR assay (<400 copies/mL) in
approximately 80% of patients in both the TID dosing group (58/75) and the
combined BID dosing group (165/204) and has remained below the limit of
detection in 74% of the first patients in both groups (TID: 23/31; BID: 62/84)
to have received treatment for 32 weeks. Mean CD4+ T-cell counts (infection-
fighting cells of the immune system) increased 181 and 155 cells/mm3 in the
combined BID group and the TID group, respectively. Prior to treatment, the
mean viral load (the amount of HIV in plasma) of patients enrolled was 4.80
log10 viral copies/mL and the mean baseline CD4+ T-cell count was 260
cells/mm3. Patients enrolled in this study had less than six months of prior
nucleoside antiretroviral therapy. Patients on the 750mg and 1000mg BID
dosing regimens were recently switched to the 1250mg BID dosing regimen.
VIRACEPT BID regimens were generally well tolerated. The only side effect
of moderate or greater intensity to occur in more than 5% of patients
receiving VIRACEPT was diarrhea, which occurred at a rate of 12% and 13%,
respectively, in the TID and combined BID group. 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.
These European data were generally consistent with results presented from
pilot studies conducted at five sites in the United States. Three 24-week
studies were designed to assess BID regimens of VIRACEPT in combination with
two nucleoside analogs. At baseline, the mean viral load of 46 patients in
these studies was approximately 4.9 log10 viral copies/mL; their mean CD4+ T-
cell count was 346 cells/mm3. Thirty-six patients received 1250mg VIRACEPT
BID + d4T + 3TC, or Retrovir(R) (AZT or zidovudine) + 3TC, and ten patients
received 1000mg VIRACEPT BID + AZT + 3TC.
After 24 weeks of therapy, 93% (14/15) of patients who received the 1250mg
VIRACEPT BID regimen and all patients (10/10) receiving the 1000mg VIRACEPT
BID regimen had viral loads below the limit of detection (<400 copies/mL). Of
the patients with HIV RNA below the standard assay limit of detection, 100%
(12/12) of those receiving 1250mg BID and 70% (7/10) of those receiving 1000mg
BID were also below the limit of detection of an ultrasensitive assay (<50
copies/mL). Upon completion of the 24-week study, patients who were on the
1000mg BID VIRACEPT regimen will be increased to 1250mg BID. The BID regimens
were well tolerated.
"Our goal in anti-HIV therapy is to offer maximal suppression of the virus
with convenient dosing," said Dr. Margaret Johnson of the Royal Free Hospital,
London, principal investigator of the European study. "We are very encouraged
by these early results from VIRACEPT studies, because of what the convenience
of twice daily dosing means to those who are living with HIV."
The feasibility of BID dosing of VIRACEPT was suggested by pharmacokinetic
assessments of 39 patients after 4 weeks of treatment in a European study.
Acceptable minimal plasma concentrations persisted throughout steady-state
dosing intervals for both the BID and TID regimens. Compared to the 750mg TID
regimen, the 1250mg BID regimen achieved a higher median steady-state Cmax
concentration and only a slightly lower trough concentration.
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.
Zerit(R) is a registered trademark of Bristol-Myers Squibb Company.
Retrovir(R) and Epivir(R) are registered trademarks of Glaxo Wellcome
Oncology/HIV.
AMPLICOR(TM) is a trademark of Roche Laboratories, 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
CNOC: http://www.prnewswire.com or fax, 800-758-5804, ext.
019650
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