Investigational Monoclonal Antibody Lowers HIV Load - Monoclonal Antibodies

Investigational Monoclonal Antibody Lowers HIV Load
Dec. 19, 2005
By Deborah Mitchell
WASHINGTON (Reuters Health) Dec 19 - When given with optimized background antiretroviral therapy, an investigational monoclonal antibody -- TNX-355 (Tanox, Inc.) -- significantly lowers viral load compared with placebo in highly treated HIV-infected patients.
In a late-breaker session at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Dr. Stanley T. Lewis, presented the findings of a phase II trial of TNX-355, which offers the potential of suppressing viral load while causing few, if any, side effects.
Dr. Lewis, Medical Director at Tanox, Inc., Houston and his colleagues randomly assigned 83 triple drug class-experienced patients to optimal combination antiretroviral therapy alone; optimal combination antiretroviral therapy plus 15/mg/kg TNX-355; or optimal combination therapy plus 10 mg/kg TNX-355. The study endpoint was mean change in HIV load at 24 weeks.
At follow-up the 10-mg/kg dose of TNX-355 resulted in a 0.96 log greater reduction in HIV RNA compared with placebo (p < 0.001.) The 15-mg/kg dose produced a 0.75 greater log reduction in HIV RNA compared with placebo (p = 0.003). The 10-mg/kg dose also lowered HIV RNA to less than 400 copies/mL in 22% of patients compared with none of the patients in the placebo group.
No significant reductions in CD4 cell counts or adverse effects were associated with either dose of TNX-355.
"The monoclonal antibody attaches to the second domain of the CD4 receptor and prevents the conformational changes in gp120 that are required for (HIV) to gain access to the chemokine coreceptors -- so it works before fusion," Dr. Lewis explained. It works against CCR5, CXCR4, as well as dual-tropic HIV-1, he added.
"It has been shown so far to not be immunosuppressant (and) we have not seen any of the safety signals that you might see with an antibody being introduced, such as immunogenicity and antibody-directed cellular cytotoxicity."
However, "in our monotherapy trial we saw some patients who did develop some decreased susceptibility to TNX-355 -- very similar to what you've seen with some of the chemokine coreceptor (blockers)."
He predicts that if the drug is approved, "at least initially, physicians will want to use TNX-355 in patients who are resistance to other therapies and patients who are having issues with tolerability."
"Over time, it may move up higher in the treatment paradigm. Patients are tired of side effects." Monoclonal antibodies will not necessarily prolong life, he said, but it will improve the quality of life in HIV-infected patients.
The investigators plan to submit these data to the FDA early next year and hope to begin a phase III trial by next fall.