Retreatment with Peginterferon Alfa-2a (Pegasys) Plus Ribavirin (Copegus) in Patients Not Responding to Prior Peginterferon Alfa-2b (PegIntron)/ Ribavirin Combination Therapy—The REPEAT Study

The REPEAT study evaluates a high fixed-dose induction of peginterferon alfa-2a (Pegasys) + ribavirin (Copegus), plus treatment extension beyond 48 weeks, with a standard dose for 48 weeks in nonresponders to peginterferon alfa-2b (PegIntron) + ribavirin (RBV).

The current report concerns the results of a protocol-planned efficacy analysis at the end of the 12-week induction.

Nonresponders to >/= 12 wks of therapy with approved doses of peginterferon alfa-2b (peg-IFN a-2b) + RBV who remained HCV RNA positive throughout treatment were eligible.

950 patients were randomized to 1 of 4 groups:

• Arms A and B − Peg-IFN a-2a (40KD) 360 mg/wk for 12 wks followed by 180 mg/wk for a further 60 or 36 wks, respectively;
  
  
• Arms C and D − Peg-IFN a-2a (40KD) 180 mg/wk for 72 or 48 wks, respectively.
  
  
• All pts received 1000/1200 mg/d RBV.
  
  
• HCV RNA was measured by quantitative or qualitative PCR assay.
  
  
• Pts without wk 12 HCV RNA measurements who discontinued early (for any reason) were classed as nonresponders.
  
  
• Data from arms A and B (Peg-IFN a-2a induction), and arms C and D (Peg-IFN a-2a standard dose) were combined.
  
  
• All patients have now completed 12 wks’ treatment.
  
  
• After the initial 12-week treatment period, all patients are being treated with the standard dose of Pegasys and Copegus
  
  
• To date, efficacy data from 856 pts have been analyzed.

Results (Table)

• Baseline characteristics were similar in the 2 groups.
• A greater proportion of pts treated with high fixed-dose induction of Pegasys became HCV non-quantifiable or experienced a >/= 2-log10 drop in HCV RNA by wk 12, compared with those treated with standard-dose Pegasys

In conclusion, Dr. Marcellin and colleagues write, “A high fixed-dose induction of Peg-IFN a-2a (40KD) (Pegasys) is more effective than standard-dose regimens among previous nonresponders to Peg-IFN alfa-2b (PegIntron)over the first 3 months of re-treatment.

In an announcement about the REPEAT study, presented at the 56^th AASLD, Roche states:

• Forty-five percent of patients treated with the standard dose of Pegasys with Copegus had an early viral response (EVR), defined as having a ≥ 2 log drop in viral load or having no detectable virus (n = 469). An EVR rate of 62 percent was achieved in the group of patients who were treated with the induction dose of Pegasys with Copegus for the first 12 weeks of therapy (n = 473).

"The interim results from this study suggest that previous non-responders to treatment can still be re-treated with some success, particularly in those treated with the higher dose of Pegasys with ribavirin," said Donald Jensen, MD, professor of medicine and director of the Center for Liver Diseases at the University of Chicago. "In addition, the interim data show that the high dose of Pegasys is generally well tolerated by patients."

According to Roche, additional key findings from the 12-week REPEAT results include the following:

• Fifty percent of the patients in this trial with advanced fibrosis or cirrhosis who received the induction dose of Pegasys plus Copegus achieved an early viral response (n = 119).

• There was no difference in adverse events for patients taking the high fixed-dose induction of Pegasys with Copegus for 12 weeks compared to those taking the standard dose. Fatigue, headache and nausea were the most common individual adverse events reported, occurring in a similar proportion of patients in both groups analyzed.

• Serious adverse events were uncommon, occurring in 2 percent of patients in the high-dose induction group and 4 percent of those treated with standard-dose peginterferon alfa-2a.

• During the first 12 weeks of the study, a slightly higher proportion of patients receiving high-dose compared with standard-dose peginterferon  alfa-2a discontinued treatment prematurely. Overall, a similar proportion of patients in the high-dose induction group and the standard-dose groups discontinued because of adverse events.

“Preliminary results from this study may be promising for the many patients who had believed that treatment would not work for them,” said James A. Thommes, M.D. Roche Sr. Medical Director. “Not only are all patients in REPEAT non-responders to Peg-Intron plus Rebetol, many also have other baseline characteristics of difficult to treat virus. We believe this data may show potential for patients to safely and effectively have significant early viral responses when treated with the investigational dosing strategies of Pegasys plus Copegus therapy. We are looking forward to final results in the future.”

As the REPEAT trial continues, Pegasys and Copegus will be given for either a total of 48-weeks or for a longer 72-week period.

Final results are awaited with interest.

11/14/05

Reference
P Marcellin and others. REtreatment with PEgasys® in pATients not responding to prior peginterferon alfa-2b/ribavirin (RBV) combination therapy – efficacy analysis of the 12-week induction period of the REPEAT study. Abstract 72557.56^th annual meeting of the American Association for the Study of Liver Diseases (56^th AASLD). November 11-15, 2005. San Francisco, CA.