Singapore, Jul 17, 2009: Schering-Plough 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.

 

"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., clinical instructor, department of internal medicine, Baylor College of Medicine, Houston, and lead investigator for the study.

 

In the study, the virologic benefit of vicriviroc administered once-daily as a single 30 mg tablet in combination with ritonavir-boosted atazanavir is being compared to a control group receiving Truvada (emtricitabine and tenofovir disoproxil fumarate) 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.

 

In the release the company noted that 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. 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.