Promising Results in Phase II Study of Treatment with Pegasys in HBEAG Positiv

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Promising Results in Phase II Study of Treatment with Pegasys in HBEAG Positive Chronic Hepatitis B



By Ned Brown, Pharm D



Treatment with standard interferon alfa (Peg Intron or Roferon ) or with Epivir HBV (lamivudine) has shown some success, but less than optimal effectiveness in the treatment of chronic hepatitis B (CHB). Monotherapy with Pegasys (40 kDa peginterferon alfa-2a), a branched chain pegylated form of interferon alfa-2a with improved pharmacokinetic (PK) properties, has recently been shown to be associated with increased sustained virological response rates compared to standard interferon alfa (S Zeuzem and others. New England Journal of Medicine 2000: 343:1666-1672).



However, the potential value of the improved PK properties of Pegasys for the treatment of CHB has not been demonstrated. The objective of the current study was to compare the efficacy and safety of 24 weeks of treatment with three doses of Pegasys (90, 180 and 270 mg) once weekly versus 4.5 MIU Roferon (interferon alfa-2a) given three times weekly in the treatment of CHB.



The study enrolled a total of 194 adults, previously untreated with interferon alfa or having received less than 6 months of nucleoside analogue therapy more than 6 months before entry. Patients were serum positive for HBsAg, HBeAg, HBV DNA and demonstrated biopsy-proven CHB with ALT above 2 x ULN. Patients were randomized (1:1:1:1) into 4 treatment arms: Roferon 4.5 MIU tiw, or Pegasys 90, 180 or 270 mg qw.



Patients were predominantly male (74%), Oriental (97%) with a mean age of 30.8 years and mean weight of 64.5 kg; approximately 9% of patients had cirrhosis Patients were treated for 24 weeks and are then being monitored for an additional 24 weeks. Efficacy assessments consisted of measurement of HBV DNA (using COBAS AMPLICOR HBV MONITOR Test (sensitivity 400 copies/ml), quantitative and qualitative HBeAg determinations and serum ALT. Safety is assessed by evaluation of adverse events and laboratory tests.



Study Results



Treatments were well-tolerated and no major safety concerns were noted. Interim analyses have shown that Pegasys clearly leads to a more rapid and profound reduction in quantitative HBeAg. End-of-treatment one log or greater decline in HBV DNA levels was seen more often with Pegasys 180 mg therapy compared to therapy with 4.5 MIU Roferon. Further end-of-treatment follow-up for safety and efficacy are ongoing.



Conclusion



The optimized PK properties of Pegasys appear to be associated with an improved response in patients with CHB. There have been no safety concerns identified in this patient population. Larger, randomized and controlled clinical trials of Pegasys for the treatment of patients with CHB are warranted.



11/19/01