Schering-Plough Corporation announced that the European Commission on October 30 approved 48-week standard-dose Pegintron (peginterferon alfa- 2b, 1.5 mcg/kg once weekly) and Rebetol (ribavirin, 800 - 1,400 mg daily) combination therapy for retreating adult patients with chronic hepatitis C whose prior treatment with interferon alpha (pegylated or non-pegylated) and ribavirin combination therapy or interferon alpha monotherapy did not result in a sustained response.

Pegintron and Rebet ol is the first and only pegylated interferon combination therapy approved in the European Union (EU) for retreating both hepatitis C relapsers and nonresponders.

The European Commission approval of this expanded indication for Pegintron and Rebetol results in Marketing Authorization with unified labelling that is valid in the current EU 27 member states as well as in Iceland and Norway.

"This approval is an option for the large number of hepatitis C patients who failed prior therapy because it gives them a second chance at success," said Nadine Piorkowsky, president of the European Liver Patient Association (ELPA). "These patients want to eradicate the virus and now can determine after 12 weeks of retreatment with Pegintron combination therapy whether they are likely to go on to achieve a sustained response with a 48-week course of therapy."

The approval is based on results from an ongoing non-comparative clinical study (EPIC3) in which 1,336 patients with moderate to severe fibrosis or cirrhosis who failed previous treatment with combination alpha interferon/ribavirin therapy were retreated with Pegintron combination therapy. In this study, virological response at week 12 of treatment was shown to be an important predictor for achieving a sustained virological response (SVR), with 57 percent of patients who had undetectable virus (HCV- RNA) at week 12 going on to achieve SVR with a 48-week course of therapy. Within this subgroup, the SVR rates were 59 and 47 per cent for patients who failed prior therapy with non-pegylated or pegylated interferon, respectively.

Approximately 37 per cent of patients in the study overall had undetectable virus at week 12. Importantly, patients who achieved a significant reduction in virus (greater than 2 log decrease) but did not have undetectable virus at week 12, had little chance of achieving SVR (6 percent). Overall, 23 per cent of patients in the study achieved SVR, including 16 percent of patients who failed prior peginterferon and ribavirin combination therapy. SVR is defined as undetectable HCV-RNA at 24 weeks post-treatment.

"Based on a patient's treatment history, these Pegintron data allow physicians to identify which patients in this hard-to-treat population are right for retreatment and are most likely to achieve a sustained response," said Thierry Poynard, M.D., professor of medicine, University of Paris VI, Hopital Pitie-Salpetriere, Paris, and a lead investigator of the EPIC study. "The predictability of response with Pegintron means patients with undetectable virus at week 12 have an even chance of success regardless of whether they failed previous therapy with pegylated or non-pegylated interferon and can be motivated to continue treatment, and those patients who fail to achieve an early response can have their therapy stopped with confidence."

In the study, failure to prior therapy was defined as relapse or nonresponse to one or more courses of interferon alpha plus ribavirin combination therapy (HCV-RNA positive at the end of a minimum of 12 weeks of treatment). Patients who were HCV-RNA negative at treatment week 12 continued treatment for a total of 48 weeks and were followed for 24 weeks post- treatment.

Based on results from the EPIC3 study, the recommended duration of dosing with Pegintron combination therapy for retreating patients who failed previous therapy and who have undetectable virus at week 12 is 48 weeks, regardless of HCV genotype.

Pegintron and Rebetol combination therapy was previously approved in the EU for treating chronic hepatitis C in naïve (previously untreated) adult patients, including naïve patients with clinically stable HIV coinfection. The recommended dose in the EU for combination therapy is Pegintron 1.5 mcg/kg once weekly plus Rebetol 800-1,400 mg daily, adjusted to body weight. The recommended duration of treatment is 24 weeks for naïve patients with HCV genotype 1 with low viral load and rapid virologic response (RVR) or HCV genotype 2 or 3. The recommended duration of treatment is 48 weeks for naïve patients with HCV genotype 1 and high viral load or low viral load without RVR, HCV genotype 4 or HIV coinfection regardless of HCV genotype. Pegintron had previously received centralized marketing authorization in the EU and is marketed as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C.

Chronic hepatitis C is estimated to affect more than 10 million people in major world markets, including 5 million in Europe. It is a leading cause of chronic liver disease and one of the most common reasons for liver transplant in Europe.

In the United States, Pegintron is indicated for use alone or with ribavirin for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age. Pegintron is not indicated in the United States for retreatment of patients who failed previous interferon therapy.