VANCOUVER, British Columbia - AnorMED Inc., a leader in the development of metal-based therapeutics, is progressing its lead HIV inhibitor, AMD-3100, into a Phase II clinical trial that will take place at The Johns Hopkins University School of Medicine in Baltimore, and at two additional U.S. sites.
Michael Abrams, AnorMED's president and CEO, said the trial will include 20 to 30 HIV-infected patients and is targeted to be completed by the middle of next year.
AMD-3100 emerged from a research program to evaluate the anti-HIV activity of various metal and metal-binding compounds in collaboration with the Rega Institute of Leuven, Belgium, Abrams said. It represents an entirely new class of anti-HIV agent, and studies have shown that this small molecule chemokine inhibits the binding action of HIV with the CXCR4 chemokine receptor.
The critical role of the CXCR4 receptor has only become known in the last three years. Since AMD-3100 is a relatively simple synthetic molecule with a novel mechanism of action, these properties also make it a promising drug for combining with other HIV therapies. In preclinical studies, HIV was relatively slow to develop resistance to AMD-3100 compared with other anti-HIV agents.
Although AMD-3100 is currently administered by injection, AnorMED researchers are aggressively pursuing the identification of analogs to this compound that can be administered orally. They also have a screening program to identify small molecules that inhibit other HIV-related chemokine receptors such as CCR5.
Earlier this month, AnorMED reported from a Phase I study that another one of its metal-based drugs, ZD0473, a platinum anticancer drug, showed a promising toxicity profile, paving the way for further clinical development. ZD0473 is being developed in collaboration with AstraZeneca plc, which holds the exclusive worldwide license to the drug. It is believed that ZD0473 will overcome the limitations of cisplatin and carboplatin which are currently widely used in the treatment of solid tumors, such as cancers of the lung, ovary and testes. Many of these tumors initially respond to platinum-based therapy, but in most cases the tumors become resistant and the disease recurs. In preclinical in vitro studies performed in conjunction with the Institute of Cancer Research of Sutton, U.K., it was demonstrated that ZD0473 circumvents resistance in a number of human ovarian cancer cell lines with decreased sensitivity to cisplatin. Abrams expects that Phase II studies on ZD0473 will begin later this year.