First 24-Week Results with a CCR5 Receptor Antagonist Reported TORONTO, Aug. 17 /PRNewswire-FirstCall/ -- Schering-Plough today reported that results from an ongoing Phase II clinical trial showed vicriviroc, its investigational CCR5 receptor antagonist, demonstrated potent and sustained viral suppression after 24 weeks of therapy in 118 treatment-experienced HIV patients, when administered in once-daily doses in combination with an optimized ritonavir-boosted protease inhibitor (PI)-containing antiretroviral regimen. In the study, viral load decrease was significantly greater for patients in each vicriviroc group compared to the control group at day 14 and at week 24 (p less than 0.01), and was not different between the vicriviroc groups (p greater than 0.05) (ITT). Although there was no statistical difference in the viral load reductions between the three vicriviroc arms, a higher rate of virologic failure and emergence of X4 virus was observed at the lowest dose of 5 mg. This is the first trial with a CCR5 receptor antagonist for HIV to report 24-week treatment results. Researchers from the NIH-sponsored Adult AIDS Clinical Trial Group (ACTG), which is conducting the study, presented the data here today during a late-breaker session at the XVI International AIDS Conference. "We are encouraged by the durability of viral suppression observed through 24 weeks in this study of patients with significantly advanced HIV disease," said Roy Gulick, M.D., principal investigator and associate professor, Weill Medical College of Cornell University, New York. "The promise of new antiviral agents with novel mechanisms of action and unique resistance profiles is particularly important for treatment-experienced HIV patients, who need new treatment options, and we look forward to the further clinical evaluation of vicriviroc in combination with conventional antiretroviral regimens." A total of 118 heavily treatment-experienced HIV patients (median viral load 36,380 copies/ml and CD4 146 cells/uL) with R5-type virus taking ritonavir-boosted PI-containing regimens were randomized in the double-blind, 48-week study. Change in viral load after addition of vicriviroc (5, 10 or 15 mg) dosed once daily (QD) or placebo was measured at 14 days, and then at 12 and 24 weeks, after the background antiretroviral regimen had been optimized at day 14. At day 14, the primary endpoint of the study, the mean HIV-1 RNA change from baseline (log10 copies/mL) for the vicriviroc 5, 10 and 15 mg QD arms were decreases of -0.87, -1.15 and -0.92, respectively, compared to an increase of +0.06 for the placebo arm. At week 24, the mean HIV-1 RNA change (log10 copies/mL) for vicriviroc 5, 10 and 15 mg QD arms were declines of -1.51, -1.86 and -1.68, respectively, compared to a decrease of -0.29 for the placebo arm. Mean CD4 cell counts increased at week 24 for the vicriviroc 5, 10 and 15 QD mg arms by +84, +142 and +142 respectively, compared to a decrease of -9 for the placebo group. Emergence of detectable X4-type virus was detected in 8 (27 percent), 3 (10 percent) and 2 (7 percent) of patients in the vicriviroc 5, 10 and 15 QD mg arms, compared to 1 (4 percent) in the placebo arm. Five of the 8 patients in the 5 mg QD arm demonstrated the emergence of X4 virus prior to optimization of their background regimen. The 5 mg QD dose of this trial was discontinued early due to suboptimal efficacy (patients were dose-escalated to 15 mg QD) and the study as a whole was unblinded in March 2006 after recommendation from the Study Monitoring Committee, based on reports of five malignancies (two Hodgkin's disease, one with prior Hodgkin's disease; two non-Hodgkin's disease, one with prior Hodgkin's disease; and one gastric adenocarcinoma) among vicriviroc recipients. The ACTG (including an independent safety monitoring committee) concluded causal association between vicriviroc and the malignancies could not be determined by this study. Coupled with evidence of significant virologic activity and CD4 count increases, a decision was made to continue the trial with the 10 and 15 mg doses. Open-label follow-up of patients continues; the median length of study treatment at the time of this analysis was more than 40 weeks for the 10 and 15 mg vicriviroc treatment groups. VICTOR-E1 Trial Initiated to Evaluate Higher Doses to Achieve Incremental Benefit in Treatment-Experienced HIV Patients Based on the ACTG study reported above and extensive pharmacokinetic and pharmacodynamic data, Schering-Plough Research Institute has initiated a new Phase II clinical trial of higher doses of vicriviroc in treatment-experienced HIV patients, with the goal of achieving incremental improvement in viral suppression. VICTOR-E1 (Vicriviroc in Combination Treatment with Optimized Antiretroviral Treatment Regimen in Experienced Subjects) will evaluate the safety and efficacy of vicriviroc (20 mg and 30 mg once daily) compared to placebo in combination with an optimized ritonavir-boosted, protease inhibitor-containing antiretroviral regimen. The primary objective of the study is to evaluate the antiviral activity of vicriviroc as measured by the decline of viral load (log10 copies/mL) from baseline at 12 and 24 weeks. A total of 120 patients who are currently failing an antiretroviral treatment regimen will be enrolled in the 48-week trial. The study is being conducted at sites throughout Europe and North and South America. For additional information on the ongoing VICTOR-E1 trial and trial sites, please visit http://www.clinicaltrials.gov/. About Vicriviroc Vicriviroc is an extracellular inhibitor of HIV infection that is believed to block entry of infectious virions into uninfected CD4 cells via antagonism of the CCR5 co-receptor. Despite the availability of more than 25 antiretroviral agents, the challenges of viral resistance and toxicities underscore the need for new agents with novel mechanisms of action. VICTOR-E1 and other vicriviroc studies in the drug's development program will further evaluate its utility against HIV disease when used in combination with antiretroviral drugs. Vicriviroc has been studied to date in more than 650 patients in pharmacology or clinical trials. About Schering-Plough Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 32,000 people around the world. The company is based in Kenilworth, N.J., 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 Securities Litigation Reform Act of 1995, including statements relating to the timing of clinical trials 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 about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Item 1A. Risk Factors in the Company's second quarter 2006 10-Q. 72-0806 DATASOURCE: Schering-Plough Corporation CONTACT: Media Contact - Mary-Frances Faraji, +1-908-298-7109 (office), +1-908-432-2404 (mobile); Investor Contact - Alex Kelly, or Robyn Brown, +1-908-298-7436 Web site: http://www.schering-plough.com/ http://www.clinicaltrials.gov/ Company News On-Call: http://www.prnewswire.com/comp/777050.html

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