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Schering-Plough to Initiate First Head-to-Head Study Of Leading Hepatitis C Therapies
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press release from Schering-Plough
IDEAL Trial to Compare Efficacy and Safety of Individualized, Weight-Based Dosing With PEG-INTRON® Versus Flat Dosing of PEGASYS
KENILWORTH, N.J., Sept. 23, 2003 – Schering-Plough Corporation (NYSE: SGP ) today announced plans to initiate a major clinical study involving 2,880 patients that for the first time will directly compare the two approved forms of pegylated interferon therapy1 for chronic hepatitis C virus (HCV) infection: PEG-INTRON® (peginterferon alfa-2b/Schering Corporation) versus PEGASYS (peginterferon alfa-2a/Hoffmann-La Roche, Inc.), both used in combination with ribavirin. Schering-Plough Research Institute (SPRI), in collaboration with leading medical centers, will conduct the comparative study in response to requests by the hepatitis C medical and patient communities, and to clear up misperceptions in the marketplace about these two treatments.
The IDEAL trial (Individualized Dosing Efficacy vs. flat dosing to Assess optimaL pegylated interferon therapy) will compare the efficacy and safety of individualized weight-based dosing with PEG-INTRON and REBETOL® (ribavirin, USP) versus PEGASYS, which is administered as a flat dose to all patients regardless of individual body weight, and COPEGUS (ribavirin, USP) dosed either at 1,000 mg or 1,200 mg, in U.S. patients with chronic hepatitis C, genotype 1. Genotype 1 virus is the most common worldwide, the most difficult to treat successfully and accounts for about 70 percent of HCV infection among Americans. PEG-INTRON is a form of interferon alfa-2b that has been chemically "pegylated" so it is retained in the body longer than standard interferon, thereby providing for once weekly administration. PEGASYS is a pegylated form of interferon alfa-2a.
PEG-INTRON and REBETOL combination therapy is the most-prescribed treatment for chronic hepatitis C worldwide, with more than 300,000 patients having received this treatment since its introduction in 2001.
"This is a very important study because these two treatment regimens have never before been directly compared," said John McHutchison, M.D., Medical Director, Liver Research, Duke University Medical Center, and co-principal investigator of the trial. "Findings from previous studies of PEG-INTRON and PEGASYS cannot be compared because of differences in study design, patient populations and other variables," he said.
"The IDEAL trial will include a large number of patients, providing a high degree of ‘statistical power’ to determine for the first time differences in the efficacy and safety of these two therapies," said Mark Sulkowski, M.D., Assistant Professor of Medicine, Medical Director, Viral Hepatitis Center, Division of Infectious Diseases, Johns Hopkins University School of Medicine, and co-principal investigator of the trial. "Patients infected with the hepatitis C virus and their health care providers want answers to these important questions as they seek the best available treatment options for the patient’s individual circumstances," he said.
"As the leading innovator of interferon-based treatments for hepatitis C, we are very excited about scientifically addressing this medical issue in a robust and highly powered clinical trial. We are confident that this large head-to-head study between PEG-INTRON and PEGASYS will provide valuable information that will help physicians make informed choices and provide hepatitis C patients with the best chance for achieving a sustained viral response," said Robert J. Spiegel, M.D., senior vice president of medical affairs and chief medical officer, Schering-Plough Research Institute.
PEG-INTRON and REBETOL Combination Therapy PEG-INTRON and REBETOL combination therapy is indicated for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and are at least 18 years of age.
PEG-INTRON, the only interferon product for hepatitis C approved for dosing according to body weight, is a longer-acting form of Intron® A (interferon alfa-2b, recombinant) Injection that uses proprietary PEG technology developed by Enzon, Inc. (NASDAQ: ENZN) of Bridgewater, N.J. PEG-INTRON, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy that is designed to achieve an effective balance between antiviral activity and elimination half-life. Schering-Plough holds an exclusive worldwide license to PEG-INTRON. REBETOL is an oral formulation of the antiviral agent ribavirin, a synthetic nucleoside analog.
WARNING
--REBETOL monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication. (See WARNINGS.)
--The primary toxicity of ribavirin is hemolytic anemia. The anemia associated with REBETOL therapy may result in worsening of cardiac disease that has lead to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. (See WARNINGS, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION.)
--Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple-dose half-life of 12 days, and so it may persist in nonplasma compartments for as long as 6 months. Therefore, REBETOL therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and in female partners of male patients who are taking REBETOL therapy. At least two reliable forms of effective contraception must be utilized during treatment and during the 6-month post-treatment follow-up period. (See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS-Information for Patients and Pregnancy Category X.)
--Alpha interferons, including PEG-INTRON and INTRON A, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping therapy with PEG-INTRON or INTRON A. (See WARNINGS, ADVERSE REACTIONS.)
PEG-INTRON There are no new adverse events specific to PEG-INTRON as compared to INTRON A, however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEG-INTRON were "flu-like" symptoms, occurring in approximately 50% of patients, which may decrease in severity as treatment continues. Application site disorders were common (47%), but all were mild (44%) or moderate (4%) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2% of patients receiving PEG-INTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEG-INTRON.
Psychiatric adverse events, which include insomnia, were common (57%) with PEG-INTRON, but similar to INTRON A (58%). Depression was most common at 29%. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1% of patients during or shortly after completing treatment with PEG-INTRON. PEG-INTRON is contraindicated in patients with autoimmune hepatitis and decompensated liver disease.
The following serious or clinically significant adverse events have been reported at a frequency <1% with PEG-INTRON or interferon alpha: Severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages and cotton wool spots.
Renal failure patients should be closely monitored for signs and symptoms of interferon toxicity and PEG-INTRON should be used with caution in patients with creatinine clearance <50 mL/min. Patients on PEG-INTRON therapy should have hematology and blood chemistry testing before the start of treatment and then periodically thereafter.
DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking" statements concerning, among other things, the future prospects of the company and its products, which the reader of this release should understand are subject to substantial risks and uncertainties. The company’s business prospects and the prospects of its products may be adversely affected by general market and economic factors, competitive product development, product availability, current and future branded, generic and OTC competition, market acceptance of new products, federal and state regulations and legislation, the regulatory review process in the United States and foreign countries for new products and indications, existing manufacturing issues and new manufacturing issues that may arise, timing of trade buying, patent positions, litigation and investigations, and instability or destruction in a geographic area important to the company due to reasons such as war or SARS. For further details and a discussion of these and other risks and uncertainties, see the company’s Securities and Exchange Commission filings, including the company’s 8-K filed Aug. 22, 2003.
Schering-Plough Research Institute is the pharmaceutical research and development arm of Schering-Plough Corporation, a research-based company engaged in the discovery, development, manufacturing and marketing of pharmaceutical products worldwide.
Additional Information Medical centers throughout the United States will be participating in the IDEAL trial. Future announcements will be made in approximately 5-6 weeks providing details about the study and information about trial support services offered to assist patients who want to learn more about the IDEAL trial and locate a participating center in their community.
For more information about Schering-Plough, visit the company’s website at www.schering-plough.com. For information about hepatitis, visit www.hepatitisinnovations.com.
PEGASYS and COPEGUS are trademarks of Hoffmann-La Roche Inc. See PEGASYS and COPEGUS product inserts for information on these products.
Reference:
1 National Institutes of Health. National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis C: 2002 -- June 10-12, 2002. Hepatology 2002; 36(5) Suppl 1:S3-S20.
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