AVI BioPharma Completes Clinical Trials With NeuGene Antisense Targeting Drug Metabolism
PORTLAND, Ore. - Dec. 12, 2002 - AVI BioPharma, Inc. (Nasdaq: AVII, AVIIW, AVIIZ) today announced the completion of two Phase I studies of its NeuGene® antisense drug (AVI-4557) targeting cytochrome P450 3A4. Together with an initial clinical trial completed earlier this year, these studies demonstrate that AVI's antisense drug can block cytochrome P450, a liver enzyme responsible for metabolism of more than 50 percent of currently marketed drugs. The studies also provide further evidence that NeuGene antisense drugs are safe and effective in humans.
In both of the current studies, the metabolism of a test drug, midazolam (Versed®, Roche) a preanesthetic that makes patients drowsy, was monitored before and after inhibition of cytochrome P450 3A4 by AVI-4557. Initial clinical observations showed that the first dose of midazolam made subjects drowsy as expected, the second dose of midazolam, given three days later, one day after blocking P450 3A4 with AVI-4557, made subjects sleep. This observed change in response to the test drug (a change in phenotype) was consistent with what was expected from successfully blocking drug metabolism in the subjects with antisense.
Taken together with the previous observations in the first cytochrome P450 study, which altered the metabolism of the test drug, buspirone (Buspar®, Bristol Myers), NeuGene antisense technology has been shown to be a reliable inhibitor of gene expression in human clinical studies. These observations provide further evidence that AVI's third-generation antisense is efficacious in human clinical studies, something that is difficult to prove with second-generation antisense technologies.
"We are confident that the dose, route of administration and inhibition of liver gene function may now be exploited by AVI's NeuGene technology," said Patrick L. Iversen, Ph.D., AVI's senior vice president of research and development. "AVI will continue to explore this technology in a variety of clinical settings involving the liver, including viral infections such as hepatitis C, cholesterol lowering and cancer."
Both studies were performed by MDS Pharma Services at their Belfast, Northern Ireland, site. In the first study, a 300 mg dose was administered by intravenous (IV) bolus infusion, while in the second study, 90 mg daily doses were given IV for five days. These dosing regimens respectively represent the highest single dose and the highest total dose (450 mg) of NeuGeneS ever administered to humans. This is also the first time multiple doses have been administered in human trials.
Results of the study to date indicate that these dosing regimens are safe. The injections were well tolerated, and no serious or significant adverse experiences were observed. These results permit increased flexibility in dosing in future studies.
"Our ongoing experience with AVI NeuGeneS supports their very favorable safety profile," said David H. Mason Jr., M.D., senior vice president of clinical development and regulatory affairs. "This year we have completed six NeuGene clinical trials, using a variety of dosing strategies in multiple therapeutic areas, including cancer, drug metabolism, polycystic kidney disease and cardiovascular restenosis. These studies have enrolled approximately 200 human subjects. We feel that we have demonstrated safety and effectiveness in several settings. This provides a firm foundation for our future clinical programs in cancer, cardiovascular restenosis, viral infections and metabolic diseases."
About AVI BioPharma
AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using two technology platforms: NeuGene antisense drugs and cancer immunotherapy. Its lead cancer agent, AVICINE®, a therapeutic cancer vaccine, has completed three Phase II trials in colorectal and pancreatic cancer and is initiating a Phase III pivotal trial in pancreatic cancer, with a supporting study in colorectal cancer. The first application of its NeuGene compounds, Resten-NG™, is designed to treat cancer, cardiovascular restenosis and other cell proliferation disorders by inhibiting the production of a cellular transcription factor, the oncogene c-myc. It is currently in Phase II trials for restenosis and in a Phase I/II trial for cancer. AVI has completed three Phase I NeuGene antisense studies that successfully down-regulated the liver enzyme cytochrome P450 and modified drug metabolism, and a Phase I/II trial in polycystic kidney disease. More information about AVI is available on the Company's Web site at http://www.avibio.com/.
"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: The statements that are not historical facts contained in this release are forward-looking statements that involve risks and uncertainties, including, but not limited to, the results of research and development efforts, the results of preclinical and clinical testing, the effect of regulation by the FDA and other agencies, the impact of competitive products, product development, commercialization and technological difficulties, and other risks detailed in the Company's Securities and Exchange Commission filings.