KENILWORTH, N.J., July 15 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP) today announced that it has extended to stage two an ongoing 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. In this study, vicriviroc is being evaluated in a novel nucleoside-sparing regimen that is designed to provide additional options for treatment-naive patients in a once daily regimen, while preserving other drug classes for subsequent lines of treatment.
The study is being conducted in two stages, with the first stage initiated in January 2008 and having enrolled 95 patients (47-48 per treatment arm). Following 24 weeks of treatment, a formal interim analysis was conducted and the safety results were reviewed by an independent Data Safety Monitoring Board. Based on these results, the study has been extended to stage two, in which the enrollment target is an additional 105 patients.
Unlike other classes of HIV drugs that work to inhibit viral replication within human CD4+ cells, most of which are part of the immune system, vicriviroc is an HIV entry inhibitor designed to prevent the virus from infecting healthy 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)
"CCR5 antagonists, such as vicriviroc, have a novel mechanism of action and may play a unique role as physicians seek to construct new HIV regimens to meet the specific needs of their patients," 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. "A class-sparing vicriviroc regimen for initial treatment could potentially expand options for patients by offering a new first-line therapy, while having the additional benefit of preserving the current first-line therapy and subsequent regimens for future use."
In the study, the virologic benefit of vicriviroc administered once-daily as a single 30 mg tablet in combination with ritonavir-boosted atazanavir(2) is being 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(tide) reverse transcriptase inhibitor (NRTI) class.
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.(4) 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.(5-7)
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 35 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.
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, like vicriviroc, it is administered as a once daily dose and it has been shown to have a more favorable lipid safety profile than other drugs in the PI class.
The study is being sponsored by Schering-Plough with support from Bristol-Myers Squibb.
Vicriviroc also is being studied in two large ongoing Phase III clinical studies in treatment-experienced HIV patients. For more information about vicriviroc clinical studies, please visit www.clinicaltrials.gov, search term: vicriviroc.
Key Safety Findings with Vicriviroc
A pooled data analysis was conducted for two vicriviroc Phase II studies involving 205 treatment-experienced HIV-infected patients 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. 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.(8)
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 II, Item 1A. "Risk Factors" in the Company's first quarter 2009 10-Q, filed May 1, 2009.
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 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.
5 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.
6 The DAD study group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356: 1723-35.
7 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.
8 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) 46th Annual Meeting; Oct. 25-28, 2008; Washington, D.C., USA; No. H-1269.
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