Pharmacology
Human Immunodeficiency Virus may get a new adversary at the Entry Point!
By Akanksha,Pharmacology Correspondent
Jan 17, 2005, 11:02

It is the CCR5 receptor , a co-receptor on the cell surface that, together with CD4, mediates the binding of HIV-1 and its entry into the cell. Research has shown that the CCR5 receptor is the primary co-receptor for enabling HIV-1 transmission and replication from the early stages of disease through progression to AIDS. Research also has demonstrated that people who lack a functional CCR5 receptor are resistant to HIV infection or have slower HIV/AIDS disease progression, and that blocking the biological function of CCR5 with antagonists or chemokines can inhibit HIV replication.

Researchers at Human Genome Sciences are working in direction of checking the efficacy of a monoclonal antibody developed against this CCR5 receptor. CCR5 mAb (CCR5mAb004) is a fully human monoclonal antibody that specifically recognizes and binds the chemokine receptor CCR5.

Human Genome Sciences has received clearance from the U.S. Food and Drug Administration (FDA) of its Investigational New Drug (IND) application to begin clinical trials of CCR5 mAb for the treatment of HIV/AIDS.

Human Genome Sciences now plans to proceed with a Phase 1 clinical trial to evaluate the safety, tolerability and pharmacology of CCR5 mAb in patients who are infected with HIV-1. The Phase 1 trial will be a randomized, placebo-controlled, dose-escalation, multi-center study. The primary objective of the study will be to evaluate the safety and tolerability of escalating doses of a single intravenous (IV) infusion of CCR5 mAb. The secondary objectives of the Phase 1 study will be to determine the pharmacokinetics of CCR5 mAb, and to assess its effect on plasma HIV-1 viral load and on CD4 + and CD8 + T-cell counts over time.

Preclinical studies of CCR5 mAb show that it binds specifically and with high affinity to human CCR5, prevents HIV-1 entry, demonstrates no agonistic activity or effector functions, and has a prolonged serum half-life.

David C. Stump, M.D., Executive Vice President, Drug Development, said, �I am pleased that we are now able to initiate a Phase 1 clinical trial of CCR5 mAb for use in the treatment of patients who are infected with HIV-1. HIV infection is a serious threat to health that continues to grow worldwide. There is a great need for novel therapeutic options, particularly given the continuing emergence of HIV resistance to currently available therapies. We believe that CCR5 mAb has the potential to provide a novel therapeutic option for the treatment of HIV infection and AIDS, which may offer the advantages of a lack of drug interactions and a reduced likelihood of the development of resistance.�

Craig A. Rosen, Ph.D., President and Chief Operating Officer, said, �The ability of CCR5-receptor inhibitors to block CCR5�s biological function and inhibit HIV replication has been widely reported. Our preclinical studies demonstrate that CCR5 mAb exhibits a number of characteristics that support advancing it to clinical development, including potent inhibition of CCR5-dependent entry of HIV-1 viruses into human cells, and inhibition of cell-cell fusion and viral transmission.�

H. Thomas Watkins, Chief Executive Officer, said, �Human Genome Sciences set as a milestone the goal of entering 1-2 new drugs into clinical development in 2004. The FDA�s December 2004 authorization of the first clinical study of CCR5 mAb in patients infected with HIV-1 completes our achievement of this important milestone. I am particularly pleased with the productivity of our research scientists.�

CCR5 mAb is a fully human monoclonal antibody generated by Human Genome Sciences using the Abgenix XenoMouse technology. Human Genome Sciences acquired an exclusive worldwide license from Abgenix in 2003 to develop and commercialize a fully human monoclonal antibody to the CCR5 receptor.Under the terms of a 1999 agreement, which was amended in 2001, Human Genome Sciences will pay clinical development milestone payments and royalties to Abgenix if a CCR5 mAb is successfully developed and commercialized under the agreement.CCR5 mAb will be manufactured in the Human Genome Sciences clinical manufacturing facility in Rockville, MD.

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Health professionals or patients interested in inquiring about clinical trials involving Human Genome Sciences products are requested to inquire via the Contact Us section of the web site of Human Genome Sciences.

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