Phase II VICTOR-E1 clinical study results reported

Schering-Plough Corporation (NYSE: SGP) today reported long-term data with vicriviroc, its investigational CCR5 receptor antagonist, from an ongoing, open-label extension of the Phase II VICTOR-E1 study in treatment-experienced HIV-infected patients. The results showed that vicriviroc plus optimized background therapy achieved durable virologic suppression and increased CD4 cell counts, and was generally well tolerated over two years of therapy. These 96-week results were presented at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

The study involved 85 treatment-experienced HIV-infected patients who received 48 weeks of open-label vicriviroc (30 mg once daily) plus an optimized antiretroviral regimen containing a ritonavir-boosted protease inhibitor after completion of 48 weeks of treatment in the double-blind phase of the VICTOR-E1 study (total of 96 weeks). More than half of these patients began open-label treatment with undetectable virus, i.e. an HIV-1 RNA level of less than 50 copies/mL, and about two-thirds had less than 400 copies/mL. Seventy patients remained on therapy at the time of the 96-week analysis. The virologic effect seen during the double-blind phase of the study was sustained in these patients during open-label vicriviroc treatment, with the percentage of patients achieving undetectable virus increasing over the course of therapy. Importantly, further improvements in CD4 counts were observed with longer vicriviroc therapy, with a mean increase of 50 cells/mm3 from week 48 of the double-blind study to the end of the 96-week period.

The data also showed that vicriviroc was generally well tolerated in this highly treatment-experienced population. Adverse events occurring in 5 percent or more of patients were sinusitis, cough and insomnia, consistent with findings in the double-blind phase of the VICTOR-E1 study. One patient discontinued therapy upon simultaneous diagnosis of Hodgkin's lymphoma and Kaposi's sarcoma, which were not considered treatment-related. Another patient discontinued therapy due to pregnancy. Nineteen patients experienced an adverse event of interest during the open-label portion of the study: 11 (13 percent) upper respiratory track infection, 6 (7 percent) dyslipidemia, 3 (4 percent) malignancy, 2 cardiovascular (2 percent), 1 premalignancy (1 percent) and 1 herpes simplex virus infection (1 percent). There were no treatment-emergent deaths, seizures or liver-related adverse events. Resistance to vicriviroc was infrequent and developed slowly, generally after prolonged treatment. Treatment failure occurred in 11 patients, eight of whom had one or fewer active drugs in their optimized background therapy.

"These long-term results with vicriviroc added to optimized background therapy are encouraging and show potential for durable viral suppression and sustained elevated CD4 counts in treatment-experienced HIV-infected patients," said Jihad Slim, M.D., division of infectious diseases, Saint Michael's Medical Center, Newark, N.J., and an investigator for the vicriviroc clinical program. "Importantly, vicriviroc was generally well tolerated, with most patients continuing on treatment for as long as two years."

Vicriviroc, currently in Phase III development, is an extracellular inhibitor of HIV infection. 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 a member of the CCR5 receptor antagonist class, and is designed to prevent the virus from infecting healthy CD4 cells by blocking its predominant entry route, the CCR5 co-receptor. Approximately 50-60 percent of treatment-experienced patients have virus that uses the CCR5 co-receptor.