50th AASLD - American Association for the Study of liver Diseases

NATAP at Dallas: Pegylated Interferon in Chronic HCV- Interim Data
Jules Levin, NATAP

Combination Therapy with PEG Interferon and Ribavarin in chronic HCV (phase II open-label study)- Preliminary Results 

Roche's Pegylated IFN (Pegysis)180 ug subcutaneous once a week plus oral ribavarin 1000-1200 mg bid was administered for 24-48 weeks to 20 patients (10 fasting, 10 with meals) with serologically and histologically proven chronic HCV followed by a 24 week treatment free period. Treatment could be extended to 48 weeks only for genotype 1 patients who demonstrated evidence of response (below 100 copies/ml Amplicor, 2nd generation test Roche) or normalization of ALT. Or at week 24 or for non-genotype 1 patients at the discretion of the investigator and with approval of sponsor. Serum ALT and plasma HCV RNA were monitored. Following are interim results based on only 20 patients.

To be eligible for this study patients were IFN and RBV naive men or women, serologically and histologically proven chronic hepatitis C, compensated, non-cirrhotic, persistently elevated serum ALT, and quantifiable HCV RNA (above 2000 copies/ml). Exclusion included other forms of liver disease, HIV infection, hepatocellular carcinoma, pre-existing severe depression, or other psychiatric disorder, cardiac or enal disease, seizure disorder, or retinopathy. 

Intent-to-treat analysis was performed in all 20 patients who received at least one dose of test medication. Virologic and biochemical responses were defined as no detectable HCV RNA and normal serum ALT, respectively, at various time points throughout the study. 

The incidence of adverse events was similar between fasting and non-fasting. Although most AEs were mild to moderate 4 patients experienced severe AEs. Mean hemoglobins were 15.3, 13.1, 12.6 and 12.3 g/dL, at baseline, 4, 12, and 24 weeks, respectively. Neutropenia was also observed with absolute neutrophil counts falling below 1000 cells/mm3 in 5 patients. Absolute neutrophil count began dropping from baseline but stabilized by week 4. Platelet counts declined until week 12 then stabilized; the lowest count measured was 68,000 plt/mm3. No patients required discontinuation of either test drug because of anemia, thrombocytopenia (platelets) or neutropenia. Two patients were withdrawn from treatment: one for seizure, and one for retinal hemorrhage. A total of 12 dose modifications were made in 8 pts. due to anemia (4), neutropenia (2), and other AEs (6). Through 48 weeks the most common AEs in patients were fatigue, pyrexia, myalgia (15 pts.), headache (13 pts.), insomnia & irritability (10 pts.), rigors (8 pts.), and arthralgia, dermatitis, nausea, and vomiting (7 pts.). The results of larger and randomized trials are needed to confirm these results and are ongoing or planned. Preliminary efficacy are in table below and are promising.

 The end-of -treatment (ETR) response (week 48) for patients with genotype 1 was 63% (10/16). HCV genotype 2 had sustained response rate of 100% (4/4) at week 48 (24 weeks of treatment and 24 weeks of follow-up). Studies in HIV-infected individuals are ongoing and planned. As well, on Monday data from a study of treatment of 271 cirrhotics comparing Pegysis to 3 MIU IFN 3 times per week is being reported.