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Schering-Plough Initiates Phase II Study With Vicriviroc in

April 15, 2008
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 any treatment."

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 of treatment.

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 all patients.

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 Bristol-Myers Squibb.

About Vicriviroc Ongoing Phase III Studies in Treatment-Experienced Patients

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 only.

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 Africa.

For more information about vicriviroc clinical studies, please visit 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., 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.

References

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 product.

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, DOI:10.1016/S0140-6736(08)60423-7.

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 Corporation

Web site: http://www.schering-plough.com/

http://www.clinicaltrials.gov/



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