AVI BIOPHARMA REPORTS RESULTS FROM HCV TRIAL

AVI BioPharma has reported results from a Phase II multicenter study in patients with chronic active hepatitis C virus (HCV) infection. The trial was designed to assess the safety, tolerability, pharmacokinetics and viral and clinical response to treatment with AVI's proprietary Neugene antisense compound, AVI-4065, in HCV patients.

AVI-4065 exhibited favorable safety and tolerability profiles in the 12 patients completing the clinical treatment phase of the protocol, with no serious drug-related adverse events or tolerability issues observed during treatment or follow-up. Consistent with the preliminary results, the therapeutic threshold required for efficacy of the drug was not achieved at the treatment dose used in this protocol.

Significant differences were observed in the plasma PK in patients compared with what was noted in healthy volunteers: notably, a longer plasma half life (approximately 26 hours compared with 13 hours), a lower peak plasma concentration (initially 1.2 compared with 1.6 micrograms/mL) and a slower plasma clearance (approximately 15 compared with 40 mL/minute). These observations demonstrate a direct pharmacodynamic response to HCV infection.

The peak plasma concentration (Cmax) was expected to reach the predicted therapeutic threshold of approximately 3.5 micrograms/mL during the treatment protocol, but rose to only 2.0 micrograms/mL after 14 days of therapy. With an initial Cmax of 1.2 micrograms/mL and final Cmax of 2.0 micrograms/mL, the therapeutic threshold predicted from preclinical models to be required for efficacy was not achieved.

Based on these observations AVI does not expect a clinically relevant reduction in viral titer at the treatment dose used in this protocol, nor was one observed in the 12 treated HCV patients analyzed as a group. The trend in viral responses in HCV patients dosed subcutaneously at 100 mg twice a day for 14 days was similar to that reported in preliminary data. AVI has initiated a protocol modification to increase treatment duration. The company is also in the process of planning an additional protocol to significantly increase the treatment dose in order to exceed the therapeutic threshold predicted from preclinical models.