TNX-355 Produces Significant Reduction in HIV Viral Load at 48 Weeks

Data on several investigational anti-HIV drug candidates were presented at the XVI International AIDS Conference last week in Toronto, including the latest results from a study of Tanox's investigational monoclonal antibody, TNX-355.

TNX-355 is a recombinant human antibody that binds to domain 2 of the CD4 receptor, thereby blocking the entry of HIV into host cells.

Researchers conducted a randomized, double-blind, placebo-controlled Phase II study to assess the safety and efficacy of TNX-355 versus placebo, both in combination with an optimized background regimen (OBR) of other antiretroviral drugs.

The study included 82 patients who had previously used triple-class antiretroviral therapy. Most (87%) were men, about half (46%) were white, and the mean age was 46 years. Participants were randomly assigned to receive either placebo or intravenous TNX-355 in one of two dose regimens:

10 mg/kg once weekly for 9 doses, followed by 10 mg/kg once every 2 weeks (n = 28);

mg/kg once every 2 weeks (n = 27).

If they experienced virological failure (defined as less than a 0.5 log drop in HIV RNA from baseline by week 16), patients could receive 15 mg/kg open-label TNX-355 once every 2 weeks in combination with a new OBR.

Virological and immunological responses were assessed at 24 and 48 weeks using an intent-to-treat analysis.

Results

After 24 weeks, mean reductions in HIV viral load were:

- 1.16 logs in the 10 mg/kg dose arm;
- 0.95 logs in the 15 mg/kg dose arm;
- 0.20 log in the placebo arm.

After 48 weeks, mean HIV RNA reductions were:

- 0.96 logs in the 10 mg/kg dose arm;
- 0.71 logs in the 15 mg/kg dose arm;
- 0.14 log in the placebo arm (P < 0.01).

In the TnX-355 arms, patients experienced virological failure in 230-253 days, compared with 0 days (i.e., immediate) in the placebo arm (P = 0.003).

CD4 cell count increases were greater in the TNX-355 arms (48-51 cells/mm3) compared with the placebo arm (0 cells/mm3) (P < 0.04).

No serious adverse events attributed to TNX-355, including injection site reactions, were observed.

Conclusion

In conclusion, the researchers wrote, "TNX-355 in combination with OBR resulted in a statistically significant difference in viral load reduction compared to placebo plus OBR at Week 48. Treatment with TNX-355 is associated with durable viral load reductions and clinically meaningful increases in CD4 counts in treatment-experienced patients."

8/25/06

Reference
D Norris, J Morales, E Godofsky, and others. TNX-355, in combination with optimized background regimen (OBR), achieves statistically significant viral load reduction and CD4 cell count increase when c ompared with OBR alone in phase 2 study at 48 weeks. XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract THLB0218.