Any news about the CXCR4 Entry Inhibitor AMD11070?

[xman]

AMD11070 is an oral HIV-1 entry inhibitor that targets the CXCR4 receptor on T cells. AMD11070 has been shown safe and well-tolerated in Phase I clinical trials in HIV uninfected people.

If it definitely proves effective an CXCR4 Entry Inhibitor combined with a CCR5 Entry Inhibitor should stop the whole HIV machinery rendering it unable to infect any cell in the body.

A phase I/II study was successfully completed at the end of 2008. See below:

http://clinicaltrials.gov/ct2/show/NCT00089466?term=AMD11070&rank=2

There was another trial suspended for unknown reasons but it seems not directly linked to the newer phase I/II trial

Any thoughts?

[xman]

Found the following:

BACKGROUND: The X4 Antagonist Concept Trial investigates the safety and antiviral activity of AMD11070, a potent inhibitor of X4-tropic human immunodeficiency virus (HIV) in vitro in HIV-infected patients harboring X4-tropic virus. METHODS: Patients enrolled in the study had an X4 virus population 2000 relative luminescence units (rlu; by the Monogram Trofile Assay) and an HIV-1 RNA level 5000 copies/mL. Patients received AMD11070 monotherapy for 10 days. Coreceptor tropism, plasma HIV-1 RNA level, and CD4 cell count were measured at study entry, on day 5, and on day 10. Daily predose and serial samples on the last day of treatment were obtained for determination of plasma AMD11070 concentration. RESULTS: Ten patients were given AMD11070 monotherapy (200 mg to 8 patients and 100 mg to 2 patients) twice daily for 10 days. The median baseline CD4 cell count was 160 cells/mm(3), and the median HIV-1 RNA level was 91,447 copies/mL. Four of 9 evaluable patients achieved a reduction in X4 virus population of >or= rlu. The median change in X4 virus population at the end of treatment was -0.22 log(10) rlu (range, -1.90 to 0.23 log(10) rlu). Three of 4 patients who responded to therapy showed a tropism shift from dual- or mixed-tropic viruses to exclusively R5 virus by day 10. There were no drug-related serious adverse events, adverse events of greater than grade 2, or laboratory abnormalities. CONCLUSION: These results demonstrate the activity of AMD11070, the first oral CXCR4 antagonist, against X4-tropic HIV-1. The drug was well tolerated, with no serious safety concerns. AMD11070 is on clinical hold because of histologic changes to the liver observed in long-term animal studies; additional preclinical safety assessments are pending.

[elf]

Interesting.