At the 4th International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention, held last week in Sydney, Australia, researchers presented data from a monotherapy study designed to evaluate the safety, tolerability, and antiviral activity of Incyte's investigational once-daily CCR5 antagonist, INCB009471.

The study enrolled 23 HIV positive participants with confirmed CCR5-tropic virus. They were either antiretroviral-naive or had been off treatment for at least 3 months. At baseline, the mean CD4 cell count was more than 500 cells/mm3 and the mean HIV viral load was about 4.7 log copies/mL. Subjects were randomly assigned to receive either 200 mg once-daily INCB009471 monotherapy (n = 19) or placebo (n = 4) for 14 days.

Results

• INCB009471 was safe and well tolerated.

• 21% of patients experienced any adverse events, most of which were mild-to-moderate.

• Analysis of the drug's pharmacokinetic profile on day 14 to day 16 revealed a mean minimum concentration (Cmin) 10-20 fold higher than the protein-binding-adjusted 90% inhibitory concentration (IC90) measured in peripheral blood mononuclear cells in vitro.

• The half-life of INCB009461 was about 60 hours.

• Patients receiving INCB009471 experienced rapid viral load declines, achieving reductions of 0.44 log on day 4 and 1.14 log on day 7, respectively.

• The greatest mean viral load decline, 1.82 log, occurred on day 16.

• Consistent with the long plasma half-life of INCB009471, viral load was still suppressed by 1.72 log on day 20.

• 2 weeks after the last INCB009471 dose, viral load was still suppressed by about 0.8 log relative to baseline.

• 94% of treated subjects achieved viral load declines of more than 1 log, 83% achieved declines of more than 1.5 log, and 44% achieved declines of more than 2 log.

• 42% of patients achieved viral loads below 400 copies/mL.

• CD4 cell counts were stable or increased slightly increased over the 14-day course of therapy.

• 2 patients experienced a switch in co-receptor tropism (CCR5 to CXCR4) during the study (although CXCR4-tropic virus may have existed at a low level prior to use of INCB009471).

Conclusion

"INCB009471 demonstrated potent and prolonged antiviral activity against R5-tropic HIV-1 when given once daily for 14 days," the researchers concluded. "These findings support further clinical development of INCB009471."

Community Research Initiative of New England, Boston, MA; Orlando Immunology Center, Orlando, FL; Treasure Coast Infectious Disease Consultants, Vero Beach, FL; Georgetown University Medical Center, Washington, DC; CAREID, Washington, DC; Incyte Corporation, Wilmington, DE.

07/31/07

Reference
C Cohen, E DeJesus, A Mills, and others. Potent antiretroviral activity of the once-daily CCR5 antagonist INCB009471 over 14 days of monotherapy. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Sydney, Australia, July 22-25, 2007. Abstract TUAB106.

4th IAS
Main Conference Page