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 Tanox’s monoclonal antibody, TNX-355, in 82 triple-class experienced patients (87% male, 46% Causacian, mean age 46. [1]

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 [2]), 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
N 28 27 27
Age 47 44 46
% male/female 78/22 93/7 89/11
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


  1. 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.
  2. 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.

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