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Preclinical Study Finds Protease Inhibitor-Resistant HIV May Have Reduced Potential to Develop Resistance to Panacos' Bevirimat
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WATERTOWN, Mass.--(BUSINESS WIRE)--Panacos Pharmaceuticals, Inc. (NASDAQ:PANC), a biotechnology company dedicated to developing the next generation of antiviral therapeutic products, today announced the results of a new study indicating that HIV resistant to Protease Inhibitors (PI) may have reduced potential for the development of resistance to the HIV maturation inhibitor bevirimat in laboratory assays. The study, carried out by scientists in Dr. Eric Freed's group at the HIV Drug Resistance Program at the National Cancer Institute, Frederick, MD, in collaboration with Panacos, was presented at the Cold Spring Harbor Laboratory's (CSHL) Retrovirus Conference held May 22-27, 2007 in Cold Spring Harbor, NY.
While resistance to bevirimat has not yet been reported in clinical studies, bevirimat-resistant HIV can be generated in the laboratory, as is the case with other HIV drugs. In previous studies where HIV was grown for several weeks in cell culture in the presence of bevirimat at suboptimal concentrations, mutations conferring resistance to bevirimat were found exclusively at or near bevirimat's target, the capsid-SP1 cleavage site in the HIV Gag protein. Cleavage of capsid from SP1, the final step in viral maturation, is mediated by the viral protease enzyme. Bevirimat inhibits this cleavage step by interacting with the capsid-SP1 junction in Gag, suggesting that pre-existing PI resistance mutations may have an impact on the development of bevirimat resistance.
In the new study, wild-type HIV, as well as HIV bearing major mutations conferring PI resistance, were grown in cell culture in the presence of bevirimat at suboptimal concentrations. Bevirimat resistance developed after several weeks in both wild-type and PI-resistant HIV, but took more than twice as long to develop in the PI-resistant virus. The bevirimat resistance mutation that appeared in PI-resistant virus was located at the CA-SP1 junction and has been observed previously in bevirimat resistance generation studies. The CSHL conference presentation concluded that bevirimat resistance may be less likely to arise in PI-resistant HIV strains.
Dr. Graham P. Allaway, Panacos' President and Chief Operating Officer commented, "Clinical studies to date suggest resistance to bevirimat does not develop rapidly, in contrast to some currently marketed HIV drugs, possibly because there is selective pressure to maintain the integrity of the capsid-SP1 cleavage site sequence, which is highly conserved among HIV strains. While resistance tends to develop eventually to all HIV inhibitors, the new study suggests there may be a greater hurdle to bevirimat resistance development in patients with PI-resistant virus. These patients represent one of the major groups who could potentially benefit from novel-mechanism HIV drugs such as bevirimat.h
About Panacos
Panacos is developing the next generation of anti-infective products through discovery and development of small molecule oral drugs for the treatment of HIV and other major human viral diseases. HIV infects approximately 1.7 million people in North America and Western Europe and approximately 40 million people worldwide. Approximately 650,000 patients are treated annually for HIV in the United States and Western Europe. Resistance to currently available drugs is one of the most pressing problems in HIV therapy and the leading cause of treatment failure. Panacos' proprietary discovery technologies are designed to combat resistance by focusing on novel targets in the virus life cycle, including virus maturation and virus fusion.
Panacos' lead candidate, bevirimat (PA-457), is the first in a new class of oral HIV therapeutics under development called maturation inhibitors, discovered by Panacos scientists and their academic collaborators. Based on its novel mechanism of action, bevirimat is designed to have potent activity against a broad range of HIV strains, including those that are resistant to existing classes of drugs. The Company has completed seven clinical studies of bevirimat in over 300 subjects, showing significant reductions in viral load in HIV-infected subjects and a promising safety profile, and is currently in Phase 2b clinical trials. The Company also has a second-generation program in HIV maturation inhibition in clinical testing and a research program to develop oral HIV fusion inhibitors.
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