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Positive Results Reported for Neugene Antisense Drug

PORTLAND, Ore.--(BUSINESS WIRE)--March 18, 2004--AVI BioPharma, Inc. (Nasdaq:AVII), today announced positive results from a clinical study evaluating the oral administration of its NEUGENE(R) antisense drug, AVI-4557. In the study, AVI-4557 inhibited the metabolic enzyme cytochrome P450 3A4 (CYP), a liver enzyme responsible for the metabolism or breakdown of approximately half of currently marketed drugs.

The studies were conducted in England and designed to investigate the potential of oral AVI-4557 to inhibit expression of CYP and alter the pharmacokinetics of midazolam, an anesthetic drug metabolized by CYP. The study evaluated a 10mg midazolam dose, followed by five daily oral doses of AVI-4557. On the sixth day, another dose of midazolam was administered. The primary endpoint of the study was a reduced rate of midazolam metabolism, therefore greater and longer availability of the drug in the patient's system, as demonstrated by a decrease in midazolam clearance and an increase in midazolam maximal blood concentration (Cmax).

Since the expression of CYP3A4 is highly variable from individual to individual, a paired analysis methodology was used to compare midazolam levels before and after administration of AVI-4557. The decrease in midazolam clearance was statistically significant (p=0.0251), lowering to 700 ml/min following administration of AVI-4557 from a baseline level of 877 ml/min. Further, the Cmax increased from 51 ng/ml pre-dose to 81 ng/ml post-dose, which is also statistically significant (p=0.0251). The observations demonstrate AVI-4557 reduces CYP3A4 expression.

"To our knowledge, this is the first demonstration of efficacy in a human clinical study with an oral antisense compound," said Denis R. Burger, Ph.D., chief executive officer of AVI. "By targeting this liver enzyme we were able to carefully evaluate efficacy in this study. These results lend further support to our third-generation antisense agents in other clinical programs. Our goal is to combine AVI-4557 with existing drugs that would benefit from reduced dosing levels, thereby potentially limiting toxicity without compromising efficacy."

AVI-4557 has been shown in previous human studies to inhibit the metabolism of two FDA-approved drugs metabolized by P450: midazolam and the anti-anxiety agent buspirone. Results from AVI-4557 clinical trials previously demonstrated activity when administered either by intravenous or subcutaneous routes. Preclinical tests with the drug indicate that NEUGENEs can be absorbed when given orally and can effectively inhibit their target.

Source: AVI BioPharma, Inc.

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