AVI BioPharma Reports Update of NeuGene Antisense Clinical Development Program for 2002, Plans for 2003
Third-Generation Antisense Proves Both Safe and Efficacious in Diverse Clinical Studies
PORTLAND, Ore. - Mar. 19, 2003 - AVI BioPharma, Inc. (Nasdaq: AVII, AVIIW, AVIIZ), today announced an overview of its highly successful clinical program with third-generation NeuGene® antisense for 2002, and its clinical development plans for 2003. In 2002, AVI completed six clinical trials with more than 200 patients and volunteers given third-generation antisense targeted against two different genes, the transcription factor/oncogene c-myc, and the drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4).
The six studies were quite diverse in terms of antisense targets, patient populations, trial design, dosing and routes of administration. In three trials, including a Phase Ib cancer screening trial, a Phase Ib Polycystic Kidney Disease (PKD) dose-escalating safety trial, and a controlled Phase II safety and efficacy trial in high-risk cardiovascular restenosis patients, NeuGene antisense to the c-myc target was employed. The other three trials were Phase I safety and pharmacokinetic (PK) studies in healthy volunteers demonstrating modification of drug metabolism by targeting the CYP3A4 enzyme.
Safety was evaluated in all six clinical studies. Three different routes of administration of the antisense drugs were used including intravenous, subcutaneous and intra-coronary. The doses ranged from 10 to 300 mg given as single bolus injections to multiple dosing with 90 mg for five consecutive days. Even with the wide range of clinical protocols, no drug-related adverse events were noted in any of the studies.
"The safety of the third-generation antisense agents was truly remarkable," said David H. Mason, Jr., M.D., senior vice president of clinical development and regulatory affairs at AVI. "I have monitored hundreds of clinical studies and never encountered safer drugs at this stage of development."
Efficacy was evaluated in four of the trials, including the Phase II study in cardiovascular restenosis and the Phase I studies in drug metabolism. In each of these studies, efficacy was observed. AVI reported interim results from the restenosis study showing an 80 percent reduction in the restenosis rate in the 10 mg NeuGene antisense-treated arm of the trial. In each of the three studies on drug metabolism, antisense inhibition of CYP3A4 enzyme resulted in a significant improvement to the pharmacokinetics of the two test drugs used in the studies.
"We have now proven that our third-generation NeuGene antisense is safe and efficacious in man. We have now proven efficacy in three separate well-controlled trials with two different gene targets," said Denis R. Burger, Ph.D., chief executive officer at AVI. "Based on these results, we have planned an extensive clinical program for 2003."
The company has planned three additional studies with its c-myc target including studies in restenosis, cancer and ocular indications. The company is also planning to bring three new antisense drugs targeting West Nile virus, cholesterol lowering and prostate cancer into the initial phases of clinical development this year.
"Based upon our extensive research and development evaluating the safety and efficacy of this third-generation antisense platform in over 50 separate disease models, I am confident that the safety and efficacy we are now observing in human studies will continue," said Patrick L. Iversen, Ph.D., senior vice president of research and development at AVI.
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 Ib 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 Ib 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.