Ribavarin Unbundling

This is an important development because it will allow ribivarin to be prescribed to be used in combination with any interferon. After AASLD, it seemed obvious to me that Schering was going to have to unbundle ribivarin. At AASLD Schering presented data on the combination of Pegylated Intron with ribivarin, but under current regulations you can't buy ribivarin with Peg Intron, only with Rebetron which is a package containing both Schering's brands of ribivarin & interferon.

In order to legally use Pegylated Intron with ribivarin Schering has to unbundle. However, this opens up a potential problem for ongoing and still enrolling studies. Studies randomize HCV infected persons to Pegylated Interferon + ribivarin or regular interferon+ribivarin. Since ribivarin was not available to use with Peginterferon for many individuals the only source of combination therapy of peginterferon+ribivarin was a study. As soon as the FDA approves ribivarin to be sold alone a patient does not need to enter a study to access ribivarin for this purpose.
Jules Levin, NATAP

Press Release
SOURCE: Schering-Plough Corporation

Schering-Plough Submits Supplemental NDA to Market REBETOL(R)  (Ribavirin, USP) Capsules Separately for use in Combination Therapy for  Chronic Hepatitis C

KENILWORTH, N.J., Dec. 14 /PRNewswire/ -- Schering-Plough Corporation  (NYSE: SGP - news) today announced that it submitted a supplemental New  Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA)  seeking approval to market REBETOLĘ (ribavirin, USP) Capsules separately  for use in combination with INTRONĘ A (interferon alfa-2b, recombinant)  Injection for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon or  who have relapsed following alpha interferon therapy.

REBETOL is approved in the United States for this indication as a  component of REBETRON^(TM) Combination Therapy, which contains REBETOL  Capsules and INTRON A Injection in a single package. Schering-Plough  will continue to market REBETRON Combination Therapy in the United States.

REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity. Schering-Plough has exclusive rights to market oral ribavirin for hepatitis C in all major world markets through a licensing agreement with ICN Pharmaceuticals, Inc. (NYSE: ICN - news) of Costa Mesa, Calif.

INTRON A is a recombinant version of naturally occurring alpha interferon, which has been shown to exert both antiviral and immunomodulatory effects. Schering-Plough markets INTRON A, the world's largest-selling alpha interferon, for 16 major antiviral and anticancer indications worldwide.

WARNINGS AND CONTRAINDICATIONS

Anemia associated with the use of REBETOL in combination with interferon alfa-2b (REBETRON Combination Therapy) may exacerbate symptoms of coronary disease or deteriorate cardiac function. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated. The most common adverse experiences associated with REBETRON Combination Therapy are ``flu-like'' symptoms, such as headache, fatigue, myalgia and fever, which appear to decrease in severity as treatment continues. Severe psychiatric adverse events, including depression, psychoses, aggressive behavior, hallucinations, violent behavior (suicidal ideation, suicidal attempts, suicides), and rare instances of homicidal ideation have occurred during combination REBETOL/INTRON A therapy, both in patients with and without a previous psychiatric disorder.

Combination REBETOL/INTRON A therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. Combination REBETOL/INTRON A therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (two reliable forms) during treatment and during the 6-month post-treatment follow-up period. Significant teratogenic and/or embriocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one-twentieth of the recommended human dose of REBETOL. If pregnancy occurs in a patient or partner of a patient during treatment or during the 6 months after treatment stops, physicians are encouraged to report such cases by calling (800) 727-7064.

Schering-Plough is a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.