Vicriviroc Demonstrates Potent Viral Suppression Through 48 Weeks of Therapy in ACTG Phase II Study in Treatment-Experienced HIV PatientsLongest Follow-Up Data for a CCR5 Receptor Antagonist Reported to Date
SYDNEY, Australia, July 24, 2007 /PRNewswire-FirstCall/ -- Schering-Plough Corporation today reported that results from a Phase II clinical trial showed vicriviroc, its investigational CCR5 antagonist, demonstrated potent and sustained viral suppression through 48 weeks of therapy in treatment-experienced HIV patients, when administered in once-daily doses in combination with an optimized ritonavir-boosted protease inhibitor (PI)- containing antiretroviral regimen. Vicriviroc is an extracellular inhibitor of HIV infection designed to block entry of infectious virions into uninfected CD4 cells via antagonism of the CCR5 co-receptor. These results represent the longest follow-up data reported to date for any CCR5 antagonist.
Researchers from the NIH-sponsored AIDS Clinical Trial Group (ACTG), which conducted the study, reported the data here today in an oral presentation at the International AIDS Society 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention.
At 48 weeks, patients in the 10 mg and 15 mg vicriviroc treatment groups achieved a median decrease in viral load of 1.92 and 1.44 (log10 copies/mL) and a median increase in CD4 cell count of 130 and 96 (cell/uL) from baseline, respectively. More patients in the vicriviroc groups had undetectable virus at 48 weeks (HIV-1 RNA <400/<50 copies/ml) compared to those in the placebo group (57/37 percent and 43/27 percent vs. 14/11 percent, respectively) and fewer patients in the vicriviroc groups experienced virological failure compared to those in the placebo group (27 and 33 percent vs. 86 percent, respectively).
In the study, there was no significant difference in grade 3 or 4 adverse events across the vicriviroc and placebo groups. Eight patients randomized to vicriviroc and two patients randomized to placebo developed malignancies. No cases of seizure were reported.
"These 48-week data establish the durability of viral suppression with a vicriviroc-containing regimen in treatment-experienced patients with advanced HIV disease, and are the first to demonstrate the sustained effects of a CCR5- based regimen through 48 weeks," said Roy Gulick, M.D., principal investigator and professor, Weill Medical College of , New York, who presented the data. "New antiviral agents with novel mechanisms of action and unique resistance profiles are urgently needed for this challenging patient population, and we look forward to the further clinical evaluation of vicriviroc in combination with antiretroviral regimens."
About the ACTG Phase II Study(1)
A total of 118 treatment-experienced HIV patients (median viral load 36,380 copies/ml and CD4 146 cells/uL) with R5-type virus at screening who were taking ritonavir-boosted PI-containing regimens were randomized in this double-blind, 48-week study to receive vicriviroc (5, 10 or 15 mg) dosed once daily or placebo, after the background antiretroviral regimen had been optimized at day 14. The study was conducted at 33 medical centers in the United States.
At day 14, the study primary endpoint, and 24 weeks, the secondary endpoint, median changes in HIV-1 RNA level from baseline (log10 copies/mL) were greater in the 5, 10 and 15 mg vicriviroc groups -0.87 and -1.51, -1.15 and -1.86 and -0.92 and -1.68, respectively, compared to the placebo group +0.06 and -0.29 (p<0.01). Mean CD4 cell counts increased at week 24 for the vicriviroc 5, 10 and 15 mg groups by +84, +142 and +142 respectively, compared to a decrease of -9 for the placebo group.
The 5 mg dose of vicriviroc in this trial was discontinued early (patients were unblinded and could increase their vicriviroc dose to 15 mg). In the study, eight patients on vicriviroc and two patients on placebo developed malignancies. As a result, the independent Safety Monitoring Committee recommended that patients be informed of this information, unblinded to treatment assignment and continued to be followed. Consequently, the study became open label on March 6, 2006.
About Vicriviroc Clinical Development
Building on the ACTG study reported above, Schering-Plough Research Institute is conducting an ongoing Phase II clinical trial of higher doses of vicriviroc in treatment-experienced HIV patients, with the goal of achieving further improvement in viral suppression. VICTOR-E1 (Vicriviroc in Combination Treatment with Optimized Antiretroviral Treatment Regimen in Experienced Subjects) is evaluating 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. A total of 116 patients have been enrolled in this 48-week trial at sites throughout Europe and North and South America.
Based on results from the ACTG and VICTOR-E1 Phase II clinical trials, Schering-Plough will select a dose of vicriviroc to move forward into Phase III clinical development in treatment-experienced patients.
Despite the availability of more than 20 antiretroviral agents, the challenges of viral resistance and toxicities underscore the need for new agents with novel mechanisms of action. Schering-Plough is committed to a broad clinical development program for vicriviroc to further evaluate its utility against HIV disease when used in combination with antiretroviral drugs. Vicriviroc has been studied to date in more than 750 patients in pharmacology or clinical trials.
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 approximately 33,500 people 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 timing of clinical trials, the company's 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 and a discussion of risks and uncertainties that may impact 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 2007 10-Q.
Reference: (1) Phase II Study of the Safety and Efficacy of Vicriviroc, a CCR5 Inhibitor, in HIV-1-Infected, Treatment-Experienced Patients: AIDS Clinical Trials Group 5211, Gulick et al., The Journal of Infectious Diseases, 2007;196:304-12.
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Posted: July 2007