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New HCV Drug AVI- 406 Early Data
  AVI's Stock Drops 32 Percent On Presented Hepatitis C Data
BioWorld Today - May. 11, 2006
By Aaron Lorenzo
Washington Editor
Investors fled AVI BioPharma Inc. Wednesday in reaction to very early hepatitis C data reported at the International Conference on Antiviral Research meeting, with shares in the company losing nearly a third of their value.
The stock (NASDAQ:AVII) dropped $2.36 to close at $4.90, in response to findings showing that the experimental antisense drug AVI- 4065 produced only a slight decrease in viral load (0.30 log reduction) both during and after two weeks of treatment. Investors wanted more, and the 32.5 percent stock drop was punctuated by a trading volume more than six times the daily average.
But that kind of negativity didn?t come as a shock to many at the Portland, Ore.- based company.
This is a classic example of perception vs. reality, explained Michael Hubbard, AVI's director of investor relations. They're not looking at the pharmacodynamic effect that?s going on.
It's important to note, he said, that viral responses have been assessed in only a few patients to this point five, to be precise. The trial, AVI- 4065s first in humans, will recruit 40. Also of note, no rebound effect was observed out to 28 days in those evaluated to date, and the product is accumulating in the liver, where it is binding to the virus.
Based on AVI- 4065s relatively long elimination half- life and its mechanism of action an irreversible binding to the viral genome preventing viral protein synthesis company researchers expected a slow, steady liver loading in patients with high levels of viral target in the liver. That corresponds to a very slow but steady reduction in the viral load over the drug- loading period, Hubbard told BioWorld Today.
Because the drug's peak tissue concentration would be reached in three to five half- lives, or about 33 to 55 days, the company expects to tweak the study's protocol to extend treatment to 28 days. That would be done on the fly, Hubbard said, as recruitment moves forward. Active enrollment and evaluation is ongoing, with final results expected around the end of the year.
The pharmacokinetic findings were consistent with the slow- and- steady prediction, with a significant decrease in the concentration of drug in the plasma (Cmax) among hepatitis C patients compared to normal subjects in the study's initial phase. That was consistent with an increased elimination of drug in the urine, most likely bound to the virus in the hepatitis C patients, company researchers said at the meeting in Puerto Rico, and there was a correlation between viral titer at day one and the extent of reduction in Cmax, further supporting that mechanism of elimination.
Collectively, the company said the observations demonstrate AVI- 4065s pharmacodynamic response to hepatitis C virus infection.
But investors seemed bothered by the viral load results. During the 14 days of treatment, three of the five patients had an initial decrease in viral load, while the other two exhibited little initial change in viral titer.
But what are trials for Hubbard asked rhetorically, noting that the study?s probable changes in extending treatment duration represented a prime example of using early data to shape a product?s development path.
The results came from the study's second phase, which is evaluating AVI- 4065s safety, tolerability, pharmacokinetics and viral and clinical response. Participants are split into two cohorts: one with treatment- naive hepatitis C patients, and the other made of patients who failed conventional interferon and ribavarin treatment.
The compound, born from AVI's Neugene antisense technology, has exhibited favorable safety and tolerability profiles in the five examined to date, with no serious drug- related adverse events or tolerability issues observed during treatment or follow- up. Those measures will continue to be assessed, in addition to efficacy measured by virological responses. Patients also will be monitored for four months following treatment to determine the duration of AVI- 4065's virological response, and sequencing of the viral genome will be performed to assess potential resistance.
The first phase of this study was completed in March and evaluated 31 healthy volunteers who received 14 consecutive days of treatment with AVI- 4065 at three dosage levels.
Looking broadly at the companys infectious disease programs, other efforts going forward are focused on the ebola virus, dengue fever and influenza A, including the H5N1 avian flu strain. Like hepatitis C, they are single- stranded RNA viruses, which appear to be an ideal targe for AVI's Neugene antisense technology, Hubbard said.
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