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FDA Approves New Indication for PegIntron plus Ribavirin for Certain Patients Who Failed Prior Hepatitis C Treatment

On March 11, Schering-Plough announced that the U.S. Food and Drug Administration has approved new labeling for pegylated interferon alfa-2b (PegIntron) plus ribavirin (Rebetol brand) combination therapy for treatment of chronic hepatitis C in certain patients with compensated liver disease who did not achieve sustained response to prior treatment.

With this expanded indication, PegIntron plus Rebetol becomes the first combination therapy approved for treatment-experienced individuals. FDA approval of was based on data from the EPIC 3 trial, which found that undetectable HCV viral load at week 12 of treatment was a strong predictor of sustained virological response (SVR).

Following are edited excerpts from Schering-Plough's announcement of the approval:

FDA Approves an Expanded Indication for
Peginterferon-based Combination Therapy for
Patients with Chronic Hepatitis C

Kenilworth, NJ -- March 11, 2009 -- Schering-Plough Corporation today announced that the U.S. Food and Drug Administration (FDA) has approved new labeling for PegIntron (peginterferon alfa-2b) and Rebetol (ribavirin, USP) combination therapy for treating chronic hepatitis C in patients 3 years of age and older with compensated liver disease. With approval of this expanded indication, PegIntron and Rebetol is the first and only pegylated interferon combination therapy approved in the United States that is not restricted to treatment-naive patients.

Patients less likely to benefit from retreatment after failing a course of therapy include those with previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, or HCV genotype 1 infection. It is estimated that more than 100,000 patients in the United States failed prior treatment of their hepatitis C virus (HCV) infection, representing a large and growing patient population.

"With the FDA approval of PegIntron and Rebetol combination therapy for this new indication, U.S. physicians now have a treatment option that offers a second chance for success to certain patients who failed prior therapy," said Robert J. Spiegel, MD, chief medical officer and senior vice president, Schering-Plough Research Institute. "This approval further underscores Schering-Plough's leadership and long-term commitment to developing new treatment options and innovative therapies to meet the needs of patients with hepatitis C."

Data from the clinical study supporting the approval helped to define those patient groups most likely to respond to retreatment as well as those unlikely to respond. Overall, previous relapsers, patients with HCV genotype 2 or 3, or those initially treated with non-pegylated interferon therapy achieved higher rates of sustained virologic response (SVR) [SVR is defined as achievement of undetectable HCV RNA at 24 weeks] than patients with previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, or HCV genotype 1 infection.

"Based on a patient's treatment history, physicians can identify which patients may be right for retreatment with PegIntron combination therapy and may have the best chance to achieve a sustained response," said Eugene R. Schiff, MD, director, Center for Liver Diseases, University of Miami Miller School of Medicine, and a lead investigator for the clinical study on which the approval was based. "Conversely, patients with certain treatment characteristics who are unlikely to respond to this regimen can be advised accordingly."

In the clinical study supporting the approval, achievement of undetectable virus (HCV RNA) at treatment week 12 was a strong predictor of SVR. Patients who still had detectable virus at week 12 of therapy were highly unlikely to achieve SVR.

"Patients with undetectable virus at week 12 have a better chance for success and can be motivated to continue treatment," Schiff added, "and those patients who fail to achieve an early response can have their therapy stopped with confidence, thus avoiding unnecessary treatment and potential adverse events."

The approval of PegIntron for the expanded indication is based on the results of one of the clinical studies in the EPIC 3 program: a noncomparative trial in which 2,293 adult patients with moderate-to-severe fibrosis or cirrhosis who failed previous treatment with combination alpha interferon/ribavirin were retreated with PegIntron (1.5 mcg/kg once weekly) in combination with weight-adjusted Rebetol (800-1,400 mg daily).[EPIC 3 (Evaluation of PegIntron in Control of Hepatitis C Cirrhosis), a large multicenter global clinical study evaluating the benefits of PegIntron in fibrotic and cirrhotic patients.]

Eligible patients had received at least 12 weeks of combination therapy and included prior nonresponders (patients who were HCV RNA positive at the end of a minimum 12 weeks of treatment) and prior relapsers (patients who were HCV RNA negative at the end of treatment and subsequently relapsed after post-treatment follow-up). In the study, patients who were HCV RNA negative at week 12 were treated for a total of 48 weeks and followed for 24 weeks post-treatment. Response to treatment was defined as undetectable HCV RNA at 24 weeks post-treatment.

The overall response rate in the study was 22 percent (497/2,293). Response rates among relapsers overall were 43 percent (130/300) and 35 percent (113/344) for patients previously treated with non-pegylated or pegylated alpha interferon and ribavirin combination therapy, respectively. The response rates in nonresponders overall were 18 percent (158/903) and 6 percent (30/476), respectively.

In the study, 1,470 (64 percent) patients did not achieve undetectable HCV RNA at treatment week 12, and were offered enrollment into long-term treatment trials, due to an inadequate treatment response.

Of the 823 (36 percent) patients who were HCV RNA undetectable at treatment week 12, those infected with HCV genotype 1 had an SVR rate of 48 percent (245/507), with a range of responses by fibrosis score (F4-F2) of 39-55 percent. Patients infected with HCV genotype 2 or 3 who were HCV RNA undetectable at treatment week 12 had an overall SVR of 70 percent (196/281), with a range of responses by fibrosis score (F4-F2) of 60-83 percent. For all HCV genotypes, higher fibrosis scores were associated with a decreased likelihood of achieving SVR.

The recommended treatment duration with PegIntron combination therapy for patients who failed prior treatment is 48 weeks, regardless of HCV genotype. Retreated patients who have detectable HCV-RNA at week 12 or 24 are highly unlikely to achieve SVR and discontinuation of therapy should be considered.

Patients receiving PegIntron and Rebetol as retreatment after failing a previous interferon combination regimen reported adverse reactions similar to those previously associated with this regimen during clinical trials of treatment-naive patients.

About PegIntron

In the United States, PegIntron is indicated for use in combination with ribavirin in patients 3 years of age or older, and as monotherapy in patients 18 years of age and older, for the treatment of chronic hepatitis C in patients with compensated liver disease. Patients with the following characteristics are less likely to benefit from retreatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection.

For more information about Schering-Plough, see www.schering-plough.com.

More Information about Treatment for Chronic Hepatitis C.

3/13/09

Source
Schering-Plough. FDA Approves an Expanded Indication for Peginterferon-based Combination Therapy for Patients with Chronic Hepatitis C. Press Release. March 11, 2009.