Biotech Values

[DewDiligence]

FDA Approves Pegintron for Second-Line HCV

[The data on which this approval was based were released 2.5 years ago (#msg-14373654)! The 23% SVR rate seemed impressive at the time, but VRTX has far exceeded this second-line SVR rate in the PROVE-3 study (#msg-29896176). Both Pegintron and Pegasys have a second-line label in the EU, but only Pegintron has it in the US. I doubt that this will make any difference from a commercial standpoint, however.]

http://finance.yahoo.com/news/FDA-Approves-an-Expanded-prnews-14607887.html

›FDA Approves an Expanded Indication for Peginterferon-Based Combination Therapy for Patients With Chronic Hepatitis C

March 11, 2009

New use for PEGINTRON(TM) and REBETOL® offers certain patients a second chance to achieve treatment success

KENILWORTH, N.J., March 11 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP ) today announced that the U.S. Food and Drug Administration (FDA) has approved new labeling for PEGINTRON(TM) (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, M.D., 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 nonpegylated interferon therapy achieved higher rates of sustained virologic response (SVR)(1) 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, M.D., 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 EPIC3 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).(2) 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 nonpegylated 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.‹