European Drug Regulators Approve PegIntron plus Rebetol for Retreating HCV Patients Who Failed Prior Therapy

The European Commission has approved 48-week standard dose (1.5 mcg/kg once weekly) pegylated interferon alfa-2b (PegIntron) plus 800-1,400 mg daily ribavirin (Rebetol) combination therapy for the retreatment of adult patients with chronic hepatitis C whose prior treatment with interferon alfa (pegylated or non-pegylated) plus ribavirin combination therapy or interferon alfa monotherapy did not result in a sustained virological response (SVR). 

Following are excerpts from the text of an announcement from Schering-Plough regarding the European approval of PegIntron plus Rebetol:

PegIntron and Rebetol are 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 labeling 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 (EPIC 3) in which 1,336 patients with moderate to severe fibrosis or cirrhosis who failed previous treatment with combination alfa 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 percent and 47 percent for patients who failed prior therapy with non-pegylated or pegylated interferon, respectively.

Approximately 37 percent 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 percent 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, Hôpital Pitiè-Salpêtriére, 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 do not experience an early response can have their therapy stopped with confidence."

In the study, failure to respond to prior therapy was defined as relapse or nonresponse to one or more courses of interferon alfa 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 EPIC 3 study, 48 weeks is the recommended duration of dosing with PegIntron combination therapy for retreating patients who failed previous therapy and who have undetectable virus at week 12, regardless of HCV genotype.

PegIntron in the European Union

PegIntron and Rebetol combination therapy was previously approved in the European Union for treating chronic hepatitis C in naive (previously untreated) adult patients, including naive 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 naive 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 naive 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.

11/20/07

Source
Schering-Plough. PegIntron and Rebetol Approved in European Union for Retreating Hepatitis C Patients Who Failed Previous Pegylated or Non-pegylated Interferon Therapy. Press Release. November 16, 2007.