AVI Announces Positive Interim Results of Phase II Antisense Trial For Cardiovascular Restenosis
PORTLAND, Ore. - Oct. 1, 2002 - AVI BioPharma, Inc. (Nasdaq: AVII, AVIIW, AVIIZ), has announced positive interim results of a Phase II clinical trial measuring the safety and efficacy of its antisense compound, Resten-NG™, when delivered via catheter during balloon angioplasty procedures. The results were presented Saturday at the Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington, D.C., by the trial's principal investigator, Dr. Martin Leon, senior physician at Lenox Hill Hospital, New York.
The trial was designed to assess the safety and efficacy of Resten-NG in preventing coronary artery restenosis after angioplasty and stent placement for the treatment of atherosclerotic lesions. Resten-NG targets and blocks c-myc, a regulatory gene that is the key factor in the cascade of effects that lead to restenosis in many angioplasty patients.
Data were presented for enrolled patients who have completed their six-month follow-up, including angiography and intravascular ultrasound (IVUS), to evaluate the restenosis level in patients in three study groups: a control group that received no drug treatment and two groups that received the antisense drug. The dose ranges for the antisense groups were determined from preclinical studies to be a sub-therapeutic dose (3mg) and a therapeutic dose (10mg).
Patients who received 10 mg of Resten-NG had an 11 percent restenosis rate. Patients in the control group and those who received the sub-therapeutic dose (3mg) of Resten-NG averaged approximately a 50 percent restenosis rate, which was expected in these high risk study patients. The patients who received the therapeutic dose (10mg) of Resten-NG therefore experienced approximately an 80 percent reduction in the rate of restenosis.
"We designed this study as a true test of the antisense approach to treating restenosis, enrolling patients whose health history and previous treatments predisposed them to the disease," said Patrick L. Iversen, Ph.D., senior vice president of research and development for AVI. "Although these are interim results involving a small number of patients, the reduction in restenosis levels in antisense-treated patients compared to the control groups is substantial."
Safety was evaluated by observation of adverse clinical events, particularly major adverse cardiac events (MACE) such as heart attack and the need for blood vessel or target lesion re-vascularization. Interim results indicate that Resten-NG is safe. No serious adverse events related to the drug have been observed.
"By blocking the c-myc gene, we've reduced the incidence of restenosis in patients predisposed to the disease, a crucial step in the development of Resten-NG," said Denis R. Burger, Ph.D., CEO of AVI. "These preliminary results support our contention that AVI's third-generation antisense compounds function as predicted by extensive pre-clinical studies and are clinically relevant."
AVI has now demonstrated the effectiveness of its antisense compounds in human clinical trials against two gene targets, c-myc, as implicated in restenosis and other proliferative cell disorders, and cytochrome P450, a liver enzyme responsible for the metabolic breakdown of most FDA-approved pharmaceuticals.
AVI is currently evaluating optimal delivery systems for Resten-NG in different therapeutic applications. Extensive preclinical testing has shown positive results in four different species and three different methods of delivery (drug-eluting stents, catheter delivery and targeted systemic delivery). Medtronic Inc. holds the rights for delivery of Resten-NG via medical devices (stents, catheters, etc.) for cardiovascular disease. AVI plans to initiate a human Phase II study using Resten-NG with its targeted systemic delivery technology in 2003.
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 recently completed a Phase I NeuGene antisense study that successfully down-regulated the liver enzyme cytochrome P450 and modified drug metabolism, and also recently completed 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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