Three-class experienced patients experience 1 log viral load reduction using monoclonal antibody TNX-355
Simon Collins, HIV i-Base
The late-breaker session also included a presentation of 48-week results from Tanoxs monoclonal antibody, TNX-355, in 82 triple-class experienced patients (87% male, 46% Causacian, mean age 46. 
TNX-355 is a humanised monoclonal antibody that binds to domain 2 of the CD4 receptor, blocking entry of HIV-1 into target cells. This randomised, double-blind, placebo-controlled study used two doses of TNX-355 plus optimised background regimen (OBR) compared to placebo plus OBR. The primary endpoint was mean change in viral load at week 24 (reported at ICAAC last year ), with additional safety and efficacy data presented in this analysis through to week 48.
TNX-355 was given intravenously 10mg/kg once-weekly for 9 weeks followed by either 10mg/kg. 15mg/kg or placebo every 2 weeks. All patients received OBR. After virologic failure (< 0.5 log10 drop from baseline after week 16), patients received 15 mg/kg open-label TNX-355 every two weeks in combination with new OBR. This was a generally male, Caucasian study, with CD4 counts 200-300 cells/mm3 and viral load 4.8 logs. Further baseline characteristics are detailed in Table 1.
Both TNX-355 arms showed sustained viral load reductions of 0.7 to 0.9 logs at week 48 compared to placebo, which was matched by mean CD4 increases of around +50 cells/mm3 (detailed in Table 1). Time to loss of virologic response (TLVR) was 230 and 253 days in the 10mg and 15mg arms respectively, compared to 0 days in the placebo group. Although all groups received OBR, T-20 was not allowed in the study, and details on the use of OBR drugs were not presented.
Table 1: Baseline characteristics and ITT responses to TNX-355
|15mg/kg + OBR||10mg/kg + OBR||placebo + OBR|
|Baseline CD4 (%<200)||229 (26%)||223 (51%)||245 (43%)|
|Baseline VL (%>5log)||4.8 (26%)||5.0 (57%)||4.8 (33%)|
|Mean change in CD+||+51 (p=0.016)||+48 (p=0.031)||+1|
|Mean VL change wk 48||-0.71 (p<0.010)||-0.96 (p<0.001)||-0.14|
- Norris D, Morales J, Godofsky E et al. TNX-355, in combination with optimized background regimen (OBR), achieves statistically significant viral load reduction and CD4 cell count increase when compared with OBR alone in phase 2 study at 48 Weeks. Late breaker abstract THLB0218.
- Godofsky E, Zhang X, Sorenson M, et al. In vitro antiretroviral activity of the humanized anti-CD4 monoclonal antibody, TNX-355, against CCR5, CXCR4, and dual-tropic isolates and synergy with enfuvirtide. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy. December 16-29, 2005. Washington, DC. Abstract LB-26. See report in HTB Jan/Feb 2006.