Interim Results of a Pilot Study of the Combination of Consensus Interferon and Interferon Gamma in HCV Nonresponders to Peginterferon Alfa 2 Plus Ribavirin

Treatment of HCV with PEG IFN alfa 2 (Pegasys and PEG-Intron) plus ribavirin leads to a sustained virologic response in approximately 50% of patients. Response can be predicted at week 12 by assessment of serum HCV RNA concentrations.

Patients who have not had at least a 2 log₁₀ drop in HCV RNA by week 12 have a 97-100% chance of not responding to therapy. These patients have been termed “Null Responders” to PEG IFN alfa 2 therapies.

Preclinical studies have demonstrated strong synergistic antiviral and immunomodulatory effects of the combination of IFN alfacon-1 and IFN gamma-1b in pre-clinical models of HCV.

Given these data, researchers initiated a pilot study in 32 Null Responders to pegylated IFN alfa 2 + ribavirin.

32 patients were retreated with IFN alfacon-1, 15 mcg SQ daily, and IFN gamma-1b 50 mcg SQ TIW for 48 weeks. All patients had previously received PEG IFN alfa 2 and ribavirin for 12 weeks, and did not have at least a 2- log₁₀ drop in HCV RNA (Null Responders).

Following the initiation of combination therapy with IFN-alfacon-1 and IFN-gamma 1b, serum HCV RNA was assessed at week 12 to determine EVR and will be assessed at weeks 24, 48 and 72 to determine viral kinetics and sustained virologic responses.

Patients were monitored for constitutional symptoms and bloods were collected for serum chemistries and hematological evaluations.

Results

At the end of 12 weeks of therapy, 12 of 32 (38%) of these Null responder patients had undetectable HCV RNA (RT-PCR), and a total of 20 of 32 (65%) of the patients had either a 2 log₁₀ or greater decline in viral load or were HCV RNA negative.

Assessment of the quantitative changes in HCV RNA from baseline demonstrated that these patients as a group had a significant reduction from a mean of 11.950,000 ± 231,300 copies/mL at baseline to a mean of 87,000 ± 36,600 copies/mL at week 12 (P<0.001).

All 32 patients had a reduction from baseline in serum ALT and by week 12, all patients had ALT values that were below the upper limit of normal. There were 4 patients supported by Filgrastim for reductions in ANC.

No reductions in hemoglobin were observed.

In conclusion, the authors write, “Retreatment of PEG IFN alfa 2 + ribavirin Null Responders with the combination of IFN-alfacon-1 and IFN-gamma 1b is well tolerated, and preliminary analysis of early virologic response suggest that this treatment may be of potential benefit in these difficult to treat patients. Further study in a larger patient population is now being initiated.”

05/17/04

Reference
C B Leevy and others. [powerpoint]  Interim Results of a Pilot Study of the Combination of Type 1 (IFN alfacon-1) and Type 2 (IFN gamma-1b) Interferons in Chronic Hepatitis C Patients Who Have Failed to Respond to Peg-interferon Alpha 2 Plus Ribavirin. Abstract 124 (oral). Digestive Disease Week 2004. May 15-20. New Orleans, LA.