KENILWORTH, N.J., Feb. 10 /PRNewswire-FirstCall/ -- Schering-Plough Corporation presented data from several clinical studies in the ongoing development of vicriviroc, its investigational CCR5 receptor antagonist, at the 13th Conference on Retroviruses and Opportunistic Infections in Denver, Colorado. Vicriviroc is currently being evaluated in an ongoing Phase II clinical study in treatment-experienced HIV patients.
Data from the company’s Phase II clinical study in treatment-naive HIV patients was the subject of an oral presentation by Wayne L. Greaves, M.D., Senior Director of Global Clinical Development, Schering-Plough Research Institute. Schering-Plough had terminated this study in October 2005 when patients who received vicriviroc in combination with Combivir experienced virologic breakthrough, compared to those who received the control regimen of Combivir and efavirenz, a current standard of care for treatment-naive patients living with HIV.
In this study of 92 treatment-naive patients, vicriviroc was shown to be well tolerated, with no evidence of hepatotoxicity. A clear dose response to treatment at two weeks as measured by the decline of viral load (HIV RNA) was observed, proving a strong predictor of sustained virologic response throughout the study. Shifts in tropism (R5 virus shift to dual mixed) were infrequent in this trial and observed in all treatment groups including placebo, with subsequent optimal highly active antiretroviral treatment (HAART) resulting in viral suppression. Finally, the optimal dose and background regimen for use with vicriviroc in this patient population requires further study.
“These results have proven instructive to the further development of vicriviroc and will inform our plans for designing additional studies. While the optimal dose of vicriviroc and its role in antiretroviral regimens require further evaluation, vicriviroc was shown to be well tolerated by patients in this trial with no marked safety concerns - specifically, no liver toxicity,” said Wayne Greaves, M.D. “Further, separate drug interaction studies with commonly used protease inhibitors showed no need for dose adjustment for vicriviroc, which bodes well for studying vicriviroc in various protease inhibitor containing treatment regimens in our future trials.”
Treatment-Naive Study and Results
In this trial, CCR5-tropic patients with HIV from 22 sites throughout Europe and Canada were randomized to receive vicriviroc 25, 50, 75 mg or a placebo once daily for 14 days, before adding Combivir to their regimens. Patients who received placebo were given efavirenz in addition to their Combivir regimen. The endpoints of this 48-week trial included mean change in log10 HIV RNA (the amount of virus in the blood) from baseline at two weeks, the proportion of patients with greater than 1 log decrease, the proportion of patients with HIV RNA less than 50 and less than 400 copies per milliliter, and the mean change in CD4 count from baseline. Mean duration of patient follow-up was 31.8 weeks (1-53.8 week range). Primary analysis at two weeks showed a mean decrease in HIV RNA of 0.93 log10 in the 25 mg arm, 1.18 in the 50 mg arm, 1.34 in the 75 mg arm, and 0.07 in the placebo arm (p value less than 0.001) for each vicriviroc arm vs. placebo). The proportion of patients who experienced virologic breakthrough (RNA greater than or equal to 50 copies/mL) was 4 percent (1/24) in the placebo group, 56 percent (13/23) in the 25 mg group, 41 percent (9/22) in the 50 mg group, and 17 percent (4/23) in the 75 mg group (p value less than 0.001, pooled vs. control). Mean change in CD4 count from baseline at week two was an increase of 24 cells/uL in the 25 mg group, 85 cells/uL in the 50 mg group, 90 cells/uL in the 75 mg group, and 3 cells/uL in the placebo group (p value less than 0.001 for 50 and 75 mg vicriviroc arms vs. placebo).
Drug Interaction Studies
The results of drug interaction studies with vicriviroc and ritonavir- boosted protease inhibitors was the subject of another presentation by Schering-Plough researchers. Vicriviroc was studied in combination with ritonavir-boosted atazanavir, fosamprenavir, indinavir, nelfinavir, and saquinavir. There were no significant changes in vicriviroc plasma concentrations when combined with the protease inhibitor combinations. Regardless of whether a protease inhibitor affected other CYP450 enzymes or p- Gp, no change in effect on vicriviroc exposure was observed with the additional protease inhibitor vs. that observed with ritonavir alone. All three-agent combinations were well tolerated. Therefore, vicriviroc may be studied further for use in ritonavir-boosted protease inhibitor-containing regimens without dose adjustment or therapeutic drug monitoring.
Ongoing Development Program
Schering-Plough continues its development of vicriviroc with an ongoing and fully enrolled Phase II study in U.S. treatment-experienced patients that is being conducted by the NIH-sponsored Adult AIDS Clinical Trials Group (ACTG). Schering-Plough’s first priority is patient safety and the Company will not commence patient screening into their Phase III program until all available data have been carefully evaluated.
Schering-Plough Corporation 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 30,000 people around the world. The company’s Web site is http://www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release contains certain “forward-looking” statements, including statements relating to the timing of clinical trials and the potential for vicriviroc. Forward- looking statements relate to expectations or forecasts of future events. Many factors could cause actual results to differ materially from Schering-Plough’s forward-looking statements. The forward-looking statements may be affected by general market and economic factors, uncertainties in the regulatory approval process, federal and state regulations and legislation, and other uncertainties described in the company’s Securities and Exchange Commission filings under the heading “Disclosure Notice” including the company’s third quarter 2005 10-Q. The company does not assume the obligation to update any forward-looking statement. Reference
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