15th Conference on Retroviruses and Opportunistic Infections Boston, MA February 3-8, 2008

Vicriviroc Shows Well in Treatment-Experienced Patients

February 4, 2008

By Tim Horn

Forty-eight weeks of therapy with vicriviroc, notably a 30 mg once-daily dose of the drug combined with a Norvir (ritonavir) booster, leads to greater viral load reductions compared with placebo among HIV-positive patients with limited treatment options due to drug resistance. These new data, from a clinical trial involving Schering-Plough’s experimental CCR5 inhibitor, were reported today at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.

After HIV binds to the CD4 protein on T cells, the virus must then latch onto another receptor on the cell's surface, either CCR5 or CXCR4. Vicriviroc, like Pfizer’s approved twice-daily entry inhibitor Selzentry (maraviroc), prevents HIV from entering CD4 cells that carry the CCR5 receptor. Both drugs are largely ineffective against virus that uses, or is tropic for, the CXCR4 receptor.

The 116 patients enrolled in Schering-Plough’s Phase II VICTOR-E1 study had tried and failed drug regimens involving all three classes of oral HIV drugs and had viral loads of at least 1,000 copies while on their previous treatment regimen. The patients all had CCR5-tropic virus upon study entry, confirmed using Monogram Bioscience’s Trofile assay.

Study volunteers were randomized to once-daily vicriviroc—either 20 mg or 30 mg—with a low-dose Norvir booster, or placebo, all in combinations with an optimized background regimen (OBR) containing at least three approved HIV drugs.

The 48-week results from VICTOR-E1 were reported at CROI by Barry Zingman, MD, of Montefiore Medical Center in the Bronx, New York.

After almost a year of treatment, 14 percent of the patients had viral loads below 50 copies in the placebo group, compared with 56 percent in the 30 mg vicriviroc group and 52 percent in the 20 mg vicriviroc group. Compared with those in the placebo group, the percentages of patients with undetectable viral loads were statistically significant in both vicriviroc groups.

While patients who entered VICTOR-E1 with high viral loads were less likely to respond favorably to vicriviroc-based treatment, those who received the 30 mg dose of the drug had the best chance of sustained treatment response. Among those who entered the study with viral loads of 100,000 or higher, 33 percent in the 30 mg vicriviroc group, compared with 17 percent in the 20 mg group and 10 percent in the placebo group, had undetectable viral loads after 48 weeks.

As for patients who entered the study with viral loads below 100,000 copies, 33 percent in the placebo group, compared with 67 and 68 percent in the 30 mg and 20 mg vicriviroc groups respectively, had viral loads below 50 copies after 48 weeks.  

Given that CCR5 inhibitors target a cellular receptor instead of a viral enzyme, drug resistance is thought be much less of a problem with vicriviroc. However, patients’ viruses can switch from CCR5-tropic to CXCR4-tropic while using a CCR5 inhibitor. This was documented in 9 percent of the placebo recipients in VICTOR-E1, compared with 23 percent in the 30 mg vicriviroc group and 10 percent in the 20 mg vicriviroc group.

Virologic failures—having a viral load that failed to go undetectable or rebounded during the study—were documented in 40 percent of the placebo recipients, compared with 18 percent in the 30 mg vicriviroc group and 8 percent in 20 mg vicriviroc group.

In summary, Norvir-boosted vicriviroc plus OBR is associated with significant long-term virologic control in treatment-experienced patients. Given the more favorable treatment response using the 30 mg dose of the drug—along with additional data presented by Dr. Zingman showing that the 30 mg dose was more likely to achieve therapeutic blood levels than the 20 mg dose—the higher once-daily dose of vicriviroc should be explored more closely in Phase III studies of the drug.  

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