AMD070

AMD070 is an investigational drug belonging to a new class of drugs known as CXCR4 inhibitors. It stops the process of HIV attachment and entry into CD4 T-cells by blocking the CXCR4 co-receptor, the receptor used by the syncytium-inducing phenotype of HIV. This HIV variant is associated with a fast CD4 T-cell decline and late-stage HIV disease.

The drug was being developed by the Canadian company Anormed before its development was taken over by Genzyme.

CXCR4 is expressed on a much wider range of cell types than CCR5, and the potential for adverse effects from CXCR4 inhibition may thus be greater.

AMD070 has shown promising antiviral activity in early clinical studies, with good oral bioavailability and a favourable pharmacokinetic profile. However, while AMD070 was generally well tolerated, the drug was associated with elevated white blood cell counts and about one-quarter of participants in one study experienced tachycardia (rapid heartbeat).1 2

Another candidate being developed by the same company, AMD3451, has demonstrated antiviral activity against both CCR5-tropic and CXCR4-tropic HIV, as well as dual-tropic strains.3

References

  1. Boffito M et al. Pharmacokinetics of AMD11070, a CXCR4 antagonist, in HIV-infected patients carrying X4-tropic virus. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 571, 2007
  2. Stone ND et al. Multiple-dose escalation study of the safety, pharmacokinetics, and biologic activity of oral AMD070, a selective CXCR4 receptor inhibitor, in human subjects. Antimicrobial Agents Chemother 51: 2351-2358, 2007
  3. Princen K et al. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist. J Virol 78: 12996-13006, 2004
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