A novel monoclonal antibody, called antibody PRO 140, has been found to have a steady, potent, and dose-dependent antiviral effect in HIV patients.
Jeffrey Jacobson, M.D., of Drexel University in Philadelphia, reported the results about monoclonal antibody PRO 140 at the Interscience Conference on Anti-microbial Agents and Chemotherapy in Chicago, Illinois.
The new PRO 140 blocks HIV entry into T-lymphocytes and was found to be well tolerated in this study that tested its activity in humans for the first time.
The study, a placebo-controlled, randomized clinical trial, also showed that there were no serious drug-related adverse effects and no dose toxicity.
The antibody PRO 140 blocks the CCR5 receptor. Several similar small-molecule drugs are now on the market and or the pipeline. Some of these new drugs include maraviroc (Selzentry) and vicriviroc.
The advantage of PRO 140 is that it binds to a different part of the CCR5 receptor, allowing the CCR5 receptor to have a normal biological activity while preventing at the same time the HIV virus to enter the cell. This is certainly a clear advantage of PRO 140 over other similar monoclonal antibodies being used or tried for HIV patients.
Additionally the fact that PRO 140 binds to a different part of the CCR5 receptor will allow the possibility of using PRO 140 and other CCR5 inhibitors at the same time, potentially improving the drug response, Dr. Jacobson said
In this first human clinical trial 39 patients were enrolled. The investigators tested three doses of PRO 140 – 0.5, 2.0 and 5.0 milligrams, administered intravenously. The efficacy, tolerability, pharmacodynamics, and pharmacokinetic of the new monoclonal antibody was compared to a placebo.
The antibody PRO 140 produced a quick and prolonged reduction in viral load starting within five days. Some patients on the drug had a reduction by a factor of 10. After 10 days the average reduction was close to a factor of 1,000. Additionally, “the decline persisted for two to three weeks”, Dr. Jacobson said.
No toxic or adverse events were different from the control, although Dr. Jacobson mentioned that one patient (who was getting the highest dose) suffered fever, nausea, and vomiting within a few hours of the infusion.
Since this is the first time the new PRO 140 is tested in humans caution should be exercised. Remember that theses results come from the first time a drug is tested on humans and represent preliminary results that have not yet been subjected to peer review in medical journals.
Jacobson JM et al. “Antiretroviral Activity and Pharmacodynamics of PRO 140, a CCR5 Monoclonal Antibody, in HIV-Infected Individuals.” Presentation H-716. Interscience Conference on Anti-microbial Agents and Chemotherapy Chicago Illinois.