Monoclonal Antibody CCR5 Inhibitor PRO 140 Produces Long-lasting HIV Suppression in Single-dose Study

In order to enter human CD4 T-cells, HIV must bind to both the CD4 receptor on the cell surface and 1 of 2 co-receptors, CCR5 or CXCR4. If the virus cannot attach to a co-receptor, it cannot infect new cells. The first oral CCR5 antagonist, maraviroc (Selzentry) was recently approved, and another such agent, vicriviroc, has shown promising results in clinical trials.

Researchers have also studied another approach to blocking CCR5 co-receptor binding using CCR5 monoclonal antibodies. The idea behind this approach is that genetically engineered antibodies could attach themselves to CCR5 co-receptors, thereby rendering them unavailable for use by HIV.

A concern with this type of drug is that use of a CCR5 inhibitor could encourage the emergence of HIV that instead uses the CXCR4 co-receptor. In some studies, CXCR4-tropic HIV has been associated with more advanced disease progression.

At the recent 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, researchers reported the latest data from a study of the experimental CCR5 monoclonal antibody PRO 140, being developed by Progenics Pharmaceuticals.

In this double-blind single-dose study, 39 participants who were treatment-naive or had not received antiretroviral therapy for at least 3 months were randomly assigned to receive 0.5, 2, or 5 mg/kg of PRO 140 as monotherapy, or else placebo, via a 1-time intravenous infusion.All patients had exclusively CCR5-tropic virus at study entry.

Results

This study “provides proof of concept for PRO 140 as a potent and long-acting antiretroviral agent,” the researchers concluded. “The results strongly support future studies of multidose PRO 140 in combination with other antiretroviral drugs.”

The long period of viral load decline after dosing indicates that PRO 140 has prolonged anti-HIV activity, which may allow the drug to be administered as seldom as once every 1 or 2 weeks.

Given that IV infusion is an arduous method of administration that is likely to affect patients’ willingness to take the drug, as well as their adherence, Progenics plans further studies to see whether PRO 140 will also work when given via subcutaneous injection (similar to T-20).

Drexel Univ. Sch. of Med., Philadelphia, PA; ARCA, Atlanta, GA; Univ. of Alabama, Birmingham, AL; Univ. of Miami, Miami, FL; Albany Med. Ctr., Albany, NY; Univ. of Rochester, Rochester, NY; Univ. of Maryland, Baltimore, MD; Univ. of Cincinnati, Cincinnati, OH; Montefiore Med. Ctr., Bronx, NY; Jacobi Med. Ctr., Bronx, NY; Progenics Pharmaceuticals, Tarrytown, NY.

09/28/07

Reference

JM Jacobson, M Thompson, M Saag, and others. Antiretroviral activity and pharmacodynamics of PR0 140, a CCR5 monoclonal antibody, in HIV-infected individuals. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL. September 17-20, 2007. Abstract H-716.