Continuous Pump Infusion of Consensus Interferon in Non-respondersto HCV Therapy: pilot study

Myron Tong, Huntington Memorial Hospital Liver Center, Pasadena, CA and colleagues and InterMune, Inc., Brisbane, CA. 54th AASLD, Oct 25-29, 2003, Boston, MA

Pegylation of interferon-alfa results in an improved pharmacokinetic profile by maintaining constant blood levels, resulting in higher sustained response rates (SVR). However, modification of interferon-alfa by pegylation also reduces biologic potency. Delivery of a bio-optimized alpha interferon in an unmodified form (consensus interferon, Infergen(r)) by continuous infusion can be expected to provide sustained and constant levels of a fully potent protein.

We hypothesize that such an approach may potentially result in greater antiviral activity and improved tolerability by avoiding wide swings in interferon levels.

We conducted a phase 2 pilot study to assess the safety, tolerability and viral kinetics of Infergen (12 ug/day) by continuous infusion using a subcutaneous infusion device (Medtronic MiniMed(r) pump) in combination with ribavirin (1000 mg or 1200 mg daily). The MiniMed model 508 micro infusion pump is cleared for use in the treatment of diabetes. HCV RNA viral levels were measured at days 1, 3, 7, 10, 14, 21, 28 and then at weeks 6 and 12.

Among 10 nonresponders treated to date with Infergen by continuous infusion with available early viral kinetics data, 7 showed a substantial reduction in HCV viral levels (at least 1 log10 reduction in 4, and 2 log10 reduction in 3). All 7 of these patients were genotype 1 and 6 had less than 1.0 log10 decrease with prior treatment while 1 had a 1.5 log10 decrease at similar time-points with other combination therapy [either pegylated interferon/RBV (4 pts) or interferon-alfa/RBV (3 pts)].

No serious adverse events were reported and 3 patients discontinued (2 due to moderate interferon-related side effects and 1 due to inability to acclimate to the pump). Other patients continuing on study experienced mild adverse events that have been tolerable.

The authors concluded that consensus interferon administered by continuous delivery via the Medtronic MiniMed pump shows early substantial reduction of HCV RNA levels among nonresponder patients and shows a good safety and tolerability profile. Updated data on a total of 22 patients (including 10 naïve genotype 1 patients) will be presented.