Three-class experienced patients experience 1 log viral load reduction using monoclonal antibody TNX-355
9 September 2006. Related: Conference reports, Antiretrovirals, World AIDS 16 Toronto 2006.
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. [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 |
References:
- 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.
https://www.i-base.info/htb/3096