FDA Approves REBETRON(TM) Combination Therapy for Chronic Hepatitis C
Tenfold Increase in Sustained Response Rates Seen In Patients who Relapsed Following Alpha Interferon Monotherapy
NEW YORK, June 3 /PRNewswire/ — ICN Pharmaceuticals, Inc. (NYSE: ICN) today announced that its licensee, Schering Plough Corporation (NYSE: SGP), has received U.S. Food and Drug Administration (FDA) approval for the combination use of REBETOL(TM) (ribavirin) Capsules and INTRON(R) A (interferon alfa-2b, recombinant) Injection, to be marketed under the brand name REBETRON(TM) as combination therapy, for the treatment of chronic Hepatitis C in patients with compensated liver disease who have relapsed following alpha interferon therapy. Prior to REBETRON combination therapy, alpha interferons had been the only drugs approved in the United States for patients with Hepatitis C.
The FDA’s decision was based in part on clinical data from two pivotal multicenter Phase III studies involving patients with Hepatitis C who had relapsed following alpha interferon therapy. Results of these studies showed that REBETRON combination therapy resulted in a tenfold increase in the number of patients showing eradication of detectable [HCV-RNA (qPCR)-negative]* Hepatitis C virus (HCV) as compared to patients receiving INTRON(R) A alone.
“We are delighted by this positive news and what it means for our Company and, more important, for the many patients suffering from chronic Hepatitis C,” said Milan Panic, Chairman and Chief Executive Officer of ICN Pharmaceuticals, Inc. “We are proud to have contributed to the development of this significant therapeutic advance in a disease which represents a major public health problem.”
A Worldwide Problem
Some four million Americans are chronically infected with HCV, according to the Centers for Disease Control and Prevention (CDCP). The CDCP has estimated that 20-50 percent of chronically infected Hepatitis C patients will develop liver cirrhosis, and 20-30 percent of those will go on to develop liver cancer or liver failure requiring liver transplant. Hepatitis C infection contributes to the deaths of 8,000 to 10,000 Americans each year. This toll is expected to triple by the year 2010 and exceed the number of annual deaths due to AIDS, according to the CDCP. Similarly, in most European countries, one to two percent of the general population are chronically infected with HCV. According to a study conducted by the World Health Organization (WHO), which recently issued a world alert about the spread of Hepatitis C, as many as five million Europeans have been chronically infected with HCV.
Ribavirin is a synthetic nucleoside analog with broad-spectrum antiviral activity. ICN, which discovered ribavirin, currently markets the drug as Virazole(R) in a variety of dosage forms for at least one of 10 indications in 44 countries. Virazole(R) currently is sold in the U.S. and the E.U. only for aerosol use for the treatment of hospitalized infants and young children with lower respiratory infection due to respiratory syncytial virus (RSV). Schering-Plough has exclusive rights to market oral ribavirin for Hepatitis C in all major world markets through a licensing agreement with ICN, except in the European Union (EU), where both companies have the right to market oral ribavirin for Hepatitis C. It is expected that Marketing Authorization Applications (MAA) for the combination therapy will be submitted to the European Agency for the Evaluation of Medicinal Products (EMEA) this year.
INTRON(R) 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(R) A, the world’s largest-selling alpha interferon, for 16 major antiviral and anticancer indications worldwide.
The safety and efficacy of REBETRON combination therapy were evaluated in two identical controlled double-blind clinical trials involving 345 chronic Hepatitis C patients who had received previous treatment with alpha interferon and relapsed after having an initial response. Relapse patients were defined as patients who had a normal serum alanine aminotransferase (ALT) level at the end of up to 18 months of alpha interferon therapy with abnormal ALT values within one year following the end of the most recent course of therapy.
Patients in the clinical trials were randomized to receive subcutaneous injections of INTRON(R) A 3 million international units (MIU) three times a week and either oral ribavirin 1,000-1,200 mg daily or a matched placebo for 24 weeks of treatment. At six months post-treatment, 79 of 173 patients (45.7 percent) who received the combination therapy had undetectable virus levels* compared to 8 of 172 patients (4.7 percent) who received INTRON(R) A and placebo. Patient tolerance of the combination therapy was good, with six percent of patients treated with the combination therapy discontinuing therapy due to adverse events versus three percent of patients treated with INTRON(R) A and placebo.
The most common adverse experiences associated with combination therapy are flu-like symptoms, such as headache, fatigue, myalgia and fever, which appear to decrease in severity as treatment continues. Psychiatric disorders have been reported during combination therapy, both in patients with a previous psychiatric history and in patients with no history. These adverse events include depression, which may be severe, and rare cases of suicide ideation and suicidal attempt. REBETRON combination therapy is associated with a significant risk of abnormal fetal development. Women of childbearing potential should not begin therapy until a report of a negative pregnancy test has been obtained.
The recommended dosage of REBETRON combination therapy is 3 MIU of INTRON(R) A injected subcutaneously three times per week and 1,000-1,200 mg of ribavirin capsules administered orally in a divided daily (morning and evening) dose for 24 weeks. Patients weighing 75 kg (165 pounds) or less should receive 1,000 mg of ribavirin daily, while patients weighing more than 75 kg should receive 1,200 mg of ribavirin daily.
ICN manufactures and markets a broad range of prescription and non-prescription pharmaceuticals and biotechnology research products in over 90 countries. The Company employs over 17,000 people worldwide. ICN has operations in Western and Eastern Europe, North and Latin America, and the Pacific Rim. Additional information is available on the corporate website at http://www.icnpharm.com.
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SOURCE ICN Pharmaceuticals, Inc.
*[HCV-RNA (qPCR)-negative] is defined as less than 100 copies/ml of Hepatitis C viral RNA as measured by the National Genetics Institute assay.