Data Analysis of Up to Four Years of Treatment Presented at ICAAC/IDSA
2008 Annual Meeting
WASHINGTON, Oct. 26 /PRNewswire-FirstCall/ -- Schering-Plough
Corporation (NYSE: SGP) today reported a data analysis showing that
vicriviroc, its investigational CCR5 receptor antagonist, demonstrated
sustained viral suppression and increased CD4 cell counts and was well
tolerated through up to four years of therapy in treatment-experienced
HIV-infected patients. Vicriviroc was administered once-daily as a single
tablet in combination with an optimized antiretroviral regimen containing a
ritonavir-boosted protease inhibitor. These results represent the longest
treatment duration and clinical experience reported to date for a CCR5
receptor antagonist.
Vicriviroc, currently in Phase III development, is an extracellular
inhibitor of HIV infection designed to prevent the virus from infecting the
immune system's CD4 cells by blocking the CCR5 co-receptor. Approximately
50-60 percent of treatment-experienced patients have virus that uses the
CCR5 co-receptor.(1)
Researchers presented the data at the joint Interscience Conference on
Antimicrobial Agents and Chemotherapy (ICAAC) and Infectious Diseases
Society of America (IDSA) annual meeting.(2)
The pooled data analysis involved 205 treatment-experienced
HIV-infected patients from two vicriviroc Phase II studies who continued on
vicriviroc at the completion of 48 weeks of treatment in an open-label
extension for each study. Patients received vicriviroc for up to 216 weeks
of total treatment duration as part of an optimized antiretroviral regimen.
This analysis showed that vicriviroc was well tolerated overall, with
patients developing few complications of HIV disease. Adverse events
observed were consistent with expectations for the treatment-experienced
HIV-infected population. Importantly, the incidence of malignancy seen
across the vicriviroc clinical program has not increased over time even as
the cumulative exposure to vicriviroc has increased by numbers of patients
and duration of treatment.
"These long-term results demonstrate that vicriviroc added to an
optimized background therapy may provide durable viral suppression and
sustained elevated CD4 counts in treatment-experienced HIV-infected
patients," said Jihad Slim, M.D., division of infectious diseases, Saint
Michael's Medical Center, Newark, N.J., and an investigator for the
vicriviroc clinical program. "Importantly, vicriviroc was well tolerated,
with some patients continuing on treatment for up to four years, and it was
not associated with increased liver, CNS or cardiovascular adverse events
or with an increased incidence of malignancy in this patient population."
About the Data Analysis
Patients enrolled in the Phase II vicriviroc VICTOR-E1 study(3)
(including patients in the placebo arm) and the ACTG 5211 study(4) were
eligible to continue on open-label vicriviroc with optimized background
therapy at the completion of 48 weeks of treatment in an extension for each
study. The vicriviroc dose for all patients was escalated to 30 mg once
daily during the open-label treatment period. As there were no dose-related
differences in the safety profile, data for all patients receiving
vicriviroc were pooled for analysis regardless of the original starting
vicriviroc dose. The mean duration of vicriviroc treatment for all patients
(N=205) was 96 weeks (range 1-216 weeks).
Analyses were performed on data from all patients who completed at
least 12 weeks of vicriviroc treatment (N=196). Virologic response to
regimens containing vicriviroc was evidenced within 12 weeks by a
significant decrease in virus (HIV RNA) detectable in the blood and was
sustained long-term. Median change from baseline viral load (HIV RNA) was
-2.1, -2.2, -2.3, -2.3 (log10) at weeks 48, 96, 144 and 168, respectively.
Mean change from baseline CD4 (cells/microliter) count was +121, +144, +158
and +143 at the same time points.
Key Safety Findings
Safety analyses were performed on data from all patients who received
any vicriviroc treatment (N=205). AIDS-associated opportunistic infections
and conditions were observed infrequently and sporadically. Infections
involving the upper and lower respiratory tract were the only other
infections or adverse events that occurred in 5 percent or more of
patients. Elevations of liver enzymes and bilirubin were noted, but were
not characteristic of drug-induced liver injury and were judged to be not
related to vicriviroc. These infections and other adverse events observed
in these patients were generally consistent with expectations for patients
with advanced HIV infection and with the multiple drugs being administered.
Status of Vicriviroc Phase III Studies in Treatment-Experienced
Patients
Schering-Plough has completed patient enrollment in two large Phase III
clinical studies, known as VICTOR-E3 and VICTOR-E4 (Vicriviroc in
Combination Treatment with an Optimized Antiretroviral Therapy Regimen in
HIV-Infected Treatment-Experienced Subjects), evaluating vicriviroc 30 mg
once daily in combination with an optimized background antiretroviral
regimen containing a ritonavir-boosted protease inhibitor 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 few exclusions of commonly
prescribed drugs or need for dose adjustments based on the known vicriviroc
drug-drug interaction profile. The two studies involve a total of more than
850 patients and are currently ongoing at more than 160 sites in North
America, Latin America, Europe and South Africa.
For more information about the VICTOR-E3 and VICTOR-E4 clinical
studies, please visit http://www.clinicaltrials.gov, search term: vicriviroc.
Status of Vicriviroc Phase II Study in Treatment-Naive Patients
Schering-Plough also has completed patient enrollment in the first part
of an ongoing Phase II study of vicriviroc in a novel nucleoside-sparing
regimen for first-line therapy of adult treatment-naive HIV-infected
patients with R5-tropic virus only. Approximately 80-90 percent of
treatment-naive patients have virus that uses the CCR5 co-receptor.(5) The
study evaluates vicriviroc 30 mg once-daily in combination with
ritonavir-boosted atazanavir,(6) compared to a control group receiving
Truvada (emtricitabine and tenofovir disoproxil fumarate)(7) plus
ritonavir-boosted atazanavir, which is a currently recommended option for
first-line therapy. This novel nucleoside-sparing vicriviroc regimen is
designed to help avoid the risk of toxicities associated with the
nucleoside class of HIV drugs, 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.(8-10) This approach represents a potential
opportunity to preserve nucleoside and non-nucleoside reverse transcriptase
inhibitors (NRTIs, NNRTIs), integrase inhibitors, fusion inhibitors and
most protease inhibitors for later lines of HIV treatment. The full study
will involve approximately 200 patients and is ongoing at more than 20
sites in North America, Central America, Europe and South Africa.
For more information about the study, please visit
http://www.clinicaltrials.gov, search term: vicriviroc.
About Schering-Plough
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., USA,
and its Web site is http://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 clinical development of and the potential market 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 of these and other risks and uncertainties that may impact
forward-looking statements, see Schering-Plough's Securities and Exchange
Commission filings, including Item 8.01 of the company's 8-K filed Oct. 21,
2008.
References
(1) Coakley E, et al. Second International Workshop Targeting HIV
Entry. Oct. 20-21, 2006; Boston, MA, USA; No. 8.
(2) Dunkle LM, Greaves WL, et al. Long-Term Safety of Vicriviroc. 48th
Annual Interscience Conference on Antimicrobial Agents and Chemotherapy
(ICAAC)/Infectious Diseases Society of America (IDSA) 46 Annual Meeting;
Oct. 25-28, 2008; Washington, D.C., USA; No. H-1269.
(3) Zingman B, Suleiman J, DeJesus E, et al. Vicriviroc, a next
generation CCR5 antagonist, exhibits potent, sustained suppression of viral
replication in treatment-experienced adults: VICTOR-E1 48-week results.
15th Conference on Retroviruses and Opportunistic Infections (CROI); Feb.
3-6, 2008; Boston, MA, USA; Abstract 39LB.
(4) Gulick RM, Su Z, Flexner C, et al. Phase 2 Study of the safety and
efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-infected,
treatment-experienced patients: AIDS Clinical Trials Group 5211. J Infect
Dis. 2007;196:304-312.
(5) Hoffmann C (2007) The epidemiology of HIV coreceptor tropism. Eur J
Med Res (2007) 12: 385-390.
(6) Atazanavir sulfate is a Bristol-Myers Squibb Company prescription
medicine. Please see the atazanavir product insert for information on this
product.
(7) Truvada is a registered trademark of Gilead Sciences, Inc. Please
see the Truvada product insert for information on this product.
(8) 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.
(9) The DAD study group. Class of antiretroviral drugs and the risk of
myocardial infarction. N Engl J Med 2007; 356: 1723-35.
(10) 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. http://www.thelancet.com
published online April 2, 2008, DOI:10.1016/S0140-6736(08)60423-7.
SOURCE Schering-Plough Corporation
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Related links:
http://www.clinicaltrials.gov/
http://www.schering-plough.com
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