KENILWORTH, N.J., April 15 /PRNewswire-FirstCall/ --
Schering-Plough Corporation (NYSE:SGP) today announced that it
has initiated a Phase II clinical study with vicriviroc, its
investigational CCR5 antagonist, for use in first-line therapy of
adult treatment-naive HIV-infected patients with R5-type virus
only. Vicriviroc is a next-generation HIV entry inhibitor
designed to prevent the virus from infecting CD4 cells by
blocking its predominant entry route, the CCR5 co-receptor.
Approximately 80-90 percent of treatment-naive patients have
virus that uses the CCR5 co-receptor.(1) Vicriviroc also is being
studied in two large Phase III clinical studies in
treatment-experienced HIV patients, which are ongoing and
currently enrolling patients.
The study in treatment-naive patients evaluates the virologic
benefit of vicriviroc, administered once-daily as a single 30 mg
tablet, in combination with ritonavir-boosted atazanavir,(2)
compared to a control group receiving Truvada (emtricitabine and
tenofovir disoproxil fumarate)(3) plus ritonavir- boosted
atazanavir, which is a currently recommended option for
first-line therapy. Atazanavir is a product in the protease
inhibitor (PI) class of HIV medications. Truvada is a
combination product in the nucleoside reverse transcriptase
inhibitor (NRTI) class.
"A nucleoside-sparing vicriviroc regimen for initial treatment
may have the added strategic benefit of preserving most products
used to create a highly active antiretroviral therapy "cocktail"
for later use in patients, while also avoiding the risk of
toxicity known to be associated with the nucleoside class," said
Joseph C. Gathe, Jr., M.D., F.A.C.P., clinical instructor,
department of internal medicine, Baylor College of Medicine,
Houston, and lead investigator for the study. "This treatment
strategy could also prove beneficial for the growing number of
patients who already have primary resistance to NRTIs prior to
In previous studies in treatment-experienced HIV-infected
patients, vicriviroc in combination with an optimized
ritonavir-boosted PI-containing regimen demonstrated potent and
sustained viral suppression through 48 weeks of treatment.(4, 5)
The standard of care for treatment-naive HIV-infected individuals
is to combine three drugs from two classes to initiate
antiretroviral therapy. The combinations characteristically use
two NRTIs with either a non-nucleoside reverse transcriptase
inhibitor (NNRTI) or a ritonavir-boosted PI.(6) While these
combinations have been demonstrated to be highly effective,
long-term tolerance may be limited by the toxicity specifically
associated with nucleosides, which can include neuropathy,
myopathy, renal toxicity, hepatic steatosis, lactic acidosis,
bone marrow suppression, fat atrophy and, with certain agents,
increased risk of myocardial infarction.(7-9)
"As a next-generation HIV entry inhibitor, vicriviroc has the
potential to benefit a broad range of patients by offering potent
and sustained viral suppression, and a single once-daily dose for
use in combination with other antiretroviral agents," said Robert
J. Spiegel, M.D., chief medical officer and senior vice
president, Schering-Plough Research Institute. "CCR5 antagonists
such as vicriviroc have a novel mechanism of action in fighting
HIV, and may play a unique role as physicians seek to construct
new regimens to meet the specific needs of their patients,
whether they are starting treatment or have been treated with
several different combinations over a period of time."
About the Phase II Naive Study
This randomized, controlled, open-label study is projected to
enroll approximately 200 treatment-naive HIV-infected adult
patients at more than 20 sites in North America, Central America,
Europe and South Africa. Patients coinfected with hepatitis B or
C may be included in the study.
The primary efficacy endpoint of the study is the mean change
from baseline in viral load (log10 HIV RNA) at week 48 of
treatment. A key secondary efficacy endpoint is the proportion
of patients with plasma HIV RNA less than 50 copies/mL at week 48
The study will be conducted in two stages. In the first stage,
80 patients will be randomized (40 per treatment arm) into the
study. When the 80 subjects from the first stage have completed
24 weeks of treatment, a formal interim analysis will be
conducted and the results presented to an independent Data Safety
Monitoring Board (DSMB) to assure the safety of the study
participants. The study will be extended to stage 2 based on the
results of the 24-week interim analysis; at which time an
additional 120 patients (60 per treatment arm) will be enrolled.
The final analysis will be conducted at week 48 of treatment for
Atazanavir boosted by ritonavir was selected for use in this
study because it is recommended as an option for first-line
therapy in both the International AIDS Society and Department of
Health and Human Services guidelines for antiretroviral therapy.
Additionally, it has been shown to have a more favorable lipid
profile than other drugs in the PI class.
The study is being sponsored by Schering-Plough with support from
About Vicriviroc Ongoing Phase III Studies in
Schering-Plough is currently enrolling patients in two large
global Phase III clinical studies with vicriviroc in adult
treatment-experienced HIV-infected patients with R5-type virus
The two studies, known as VICTOR-E3 and VICTOR-E4 (Vicriviroc in
Combination Treatment with an Optimized Antiretroviral Therapy
Regimen in HIV-Infected Treatment-Experienced Subjects), evaluate
the virologic benefit of adding vicriviroc 30 mg once daily to an
optimized ritonavir-boosted PI-containing background therapy
compared to a control group receiving new optimized background
therapy alone. The optimized background therapy must include at
least two drugs to which the patient's HIV is susceptible.
Patients coinfected with hepatitis B or C may be included in
these studies and there are no exclusions of commonly prescribed
drugs or need for dose adjustments based on the known vicriviroc
drug-drug interaction profile. The two studies are currently
enrolling approximately 375 patients each at more than 160 sites
in North America, Latin America, Europe, Australia and South
For more information about vicriviroc clinical studies, please
visit www.clinicaltrials.gov, search term: vicriviroc.
Schering-Plough is an innovation-driven, science-centered global
health care company. Through its own biopharmaceutical research
and collaborations with partners, Schering-Plough creates
therapies that help save and improve lives around the world. The
company applies its research-and-development platform to human
prescription and consumer products as well as to animal health
products. Schering-Plough's vision is to "Earn Trust, Every Day"
with the doctors, patients, customers and other stakeholders
served by its colleagues around the world. The company is based
in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press
release includes certain "forward-looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements relating to the company's clinical
development plans and the potential for vicriviroc.
Forward-looking statements relate to expectations or forecasts of
future events. Schering-Plough does not assume the obligation to
update any forward-looking statement. Many factors could cause
actual results to differ materially from Schering-Plough's
forward-looking statements, including market forces, economic
factors, product availability, patent and other intellectual
property protection, current and future branded, generic or
over-the-counter competition, the regulatory process, and any
developments following regulatory approval, among other
uncertainties. For further details about these and other factors
that may impact the forward-looking statements, see Schering-
Plough's Securities and Exchange Commission filings, including
Part I, Item 1A. "Risk Factors" in Schering-Plough's 2007 10-K/A.
1 Hoffmann C (2007) The epidemiology of HIV coreceptor tropism.
Eur J Med Res (2007) 12: 385-390.
2 Atazanavir sulfate is a Bristol-Myers Squibb Company
prescription medicine. Please see the atazanavir product insert
for information on this product.
3 Truvada is a registered trademark of Gilead Sciences, Inc.
Please see the Truvada product insert for information on this
4 Vicriviroc, a next generation CCR5 antagonist, exhibits potent,
sustained suppression of viral replication in
treatment-experienced adults: VICTOR-E1 48-week results (39LB);
15th Conference on Retroviruses and Opportunistic Infections
(CROI); February 2008; Boston.
5 ACTG 5211: Phase II study of the safety and efficacy of
vicriviroc (VCV) in HIV-infected treatment-experienced subjects:
48 week results (TUAB102); International AIDS Society 4th IAS
Conference on HIV Pathogenesis, Treatment and Prevention; July
2007; Sydney, Australia.
6 Hammer SM, Schechter M, Montaner JS, et al. Treatment for adult
HIV infection: 2006 recommendations of the International AIDS
Society-USA panel. JAMA 2006; 296: 827-43.
7 Data collection on adverse events of anti-HIV drugs (DAD) study
group. Combination antiretroviral therapy and the risk of
myocardial infarction. N Engl J Med 2003; 349: 1993-2003.
8 The DAD study group. Class of antiretroviral drugs and the risk
of myocardial infarction. N Engl J Med 2007; 356: 1723-35.
9 The DAD study group. Use of nucleoside reverse transcriptase
inhibitors and risk of myocardial infarction in HIV-infected
patients enrolled in the DAD study: a multi-cohort collaboration.
www.thelancet.com published online April 2, 2008,
Source: Schering-Plough Corporation
CONTACT: Media, Robert J. Consalvo, +1-908-298-7409, or
Investors, Alex Kelly, +1-908-298-7436, both of Schering-Plough
Web site: http://www.schering-plough.com/