Coverage of CROI 2008 (Conference on Retroviruses and Opportunistic Infections)

February 4–6, 2008, Boston, MA

 

VICTOR-E1 study results raise
more questions about vicriviroc

February 4, 2008

Data were presented today on results from a study looking at the CCR5 antagonist vicriviroc (Schering-D) in people with experience taking HIV drugs. While generally positive, the results raise more questions about this drug’s future.

The VICTOR-E1 study compared two doses of vicriviroc (20mg and 30mg, both once a day) to placebo. Each dose was taken with the best available background regimen in people with extensive experience taking HIV drugs. The study was relatively small, with about 40 people in each of the three groups.

After 48 weeks, about half of the people taking either dose of vicriviroc had HIV levels below 50 copies, compared to 14% on placebo. Lower average viral loads were greater for people taking vicriviroc as well: 1.77 and 1.75 logs for the vicriviroc groups vs. 0.7 logs for placebo. Vicriviroc was generally well tolerated with few people stopping it due to intolerance.

While these results suggest fairly potent anti-HIV activity for vicriviroc, further analysis of the results raises significant questions. People with high HIV levels (above 100,000 copies/mL) at the start of the study were very unlikely to get to below 50 copies: 33% for the 30mg group, 17% for the 20mg group, and 10% for placebo. Also, many more people who took vicriviroc also took the protease inhibitor Prezista (darunavir) as part of their background regimen. At the very least, this confounds any positive results seen in this study.

A couple of years ago vicriviroc was locked in a head-to-head race with two other drugs, GSK’s aplaviroc and Pfizer’s Selzentry (maraviroc), to become the first CCR5 drug approved by the FDA. Aplaviroc’s development was halted due to rare but serious liver toxicity. Selzentry was approved a few months ago. Development of vicriviroc has been hampered by poor study results (vs. Sustiva) combined with concerns over high rates of cancer seen in some studies. The results presented at CROI are generally positive, but they do little to overcome the perception that while once promising this drug now has an uncertain future. The 30mg dose will be further developed.

Data were presented earlier in the same session on another CCR5 drug that Schering is developing called SCH532706. The results came from a single site, safety study of SCH532706 given with Norvir (ritonavir), to 12 male volunteers. After 10 days, their HIV levels were reduced an average of 1.3 logs. Interestingly HIV levels continued to decline for 5 days after the drug was stopped. There was one serious adverse event—a case of pericarditis, or inflammation of the protective sac around the heart—which may have been caused by the drug.