AVI BioPharma Study Results Reveal Increased Utility for NeuGene Antisense Drug
PORTLAND, Ore. - Feb. 20, 2003 - AVI BioPharma, Inc. (Nasdaq: AVII, AVIIW, AVIIZ) today announced data from two recently completed Phase I clinical studies that showed that a proprietary NeuGene® antisense drug (AVI-4557) had a dramatic effect on down-regulating a targeted liver enzyme.
The studies, one consisting of treatment with a single intravenous injection of 300 mg of AVI-4557 and the other consisting of treatment with five consecutive daily intravenous injections of 90 mg of AVI-4557, were designed to evaluate the safety, efficacy, and pharmacokinetics of the NeuGene in healthy human volunteers. AVI-4557 targets cytochrome P450 3A4 (CYP3A4), the human liver enzyme responsible for metabolizing more than 50 percent of current FDA approved drugs.
In both trials, AVI-4557 successfully down-regulated the targeted liver enzyme as evidenced by the significant reduction in the breakdown of the test drug, Midazolam, a preanesthetic. The inhibition of this liver enzyme in the trials effectively prevented the degradation of Midazolam so that a dose of Midazolam that was demonstrated to make trial subjects drowsy now made those same subjects sleep. These recent studies, combined with a previous trial conducted in 2002 using another test drug (Buspar), provide further proof that AVI's proprietary NeuGene antisense technology is efficacious in humans.
"These trials represent the biggest NeuGene dose and the first multiple dose regimen for NeuGeneS that AVI has administered in trials," stated Patrick L. Iversen, Ph.D., AVI's senior vice president of research and development. "The efficacy data are truly impressive, but particularly so in light of the total lack of toxicity demonstrated in both dosing regimens."
Additional analysis of the results of the trials indicated that half-life of the drug, the key determinant of dosing intervals, was increased with increasing dose and dose duration. The half-life of AVI-4557 present in the blood was nearly 11 hours for the single 300 mg dose, which was extended to nearly 27 hours after the five daily 90 mg doses. Earlier studies of smaller doses of AVI-4557 had revealed shorter half lives.
"These new findings are a very important observation in that it may be possible to achieve clinically relevant concentrations of antisense for extended periods of time," said David H. Mason, Jr., M.D., AVI's senior vice president of clinical development and regulatory affairs. "This makes treatment regimens and dosing for clinical studies much more feasible. Further studies are currently being designed to gain a greater understanding of the relationship between prevalence of the antisense target and the pharmacokinetics of the antisense drug itself."
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 P-450 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/.
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