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24 Week PegIntron/RBV Therapy Approved in Europe for HCV Genotype 1 & Low Viral Load
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Press release from Schering Plough
SHORTER COURSE OF PEG-INTRON AND REBETOL COMBINATION THERAPY APPROVED IN EUROPEAN UNION FOR CERTAIN HEPATITIS C PATIENTS WITH GENOTYPE 1 AND LOW VIRAL LOAD
KENILWORTH, N.J., Oct. 5, 2005 - Schering-Plough Corporation (NYSE: SGP) today announced that the European Commission has approved revised dosing instructions allowing for a shorter, 24-week course of PEG-INTRON (1.5 mcg/kg once weekly) and REBETOL (800 - 1,200 mg daily) combination therapy among a subgroup of patients with chronic hepatitis C virus (HCV) genotype 1 infection and low viral load (< 600,000 IU/ml) who have achieved rapid virologic response, defined as undetectable virus (HCV-RNA negative) at week 4 of treatment that is maintained through week 24. The approval follows a positive opinion granted on July 28, 2005, by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA).
Approval of this shorter PEG-INTRON and REBETOL combination treatment regimen cuts by half the duration of therapy for a subset of hepatitis C patients with genotype 1 and low viral load. This is the only treatment regimen approved in the European Union (EU) for a 24-week course of therapy in certain genotype 1 patients. In clinical studies supporting the approval, 92 percent of patients who met the criteria for early response achieved a sustained virologic response (SVR) with 24 weeks of treatment. In the United States, PEG-INTRON (1.5 mcg/kg once weekly) is approved in combination with REBETOL (800 mg daily) for a duration of treatment of 48 weeks.
"Physicians now have the opportunity to consider a shorter course of therapy for their patients with hepatitis C genotype 1 who meet specific criteria,"said Professor Stefan Zeuzem, M.D., Saarland University, Homburg, Germany, and lead investigator of the study supporting the approval. "Tailoring treatment so that those with an early response are treated for only 24 weeks rather than 48 weeks may make therapy more appealing to patients, providing comparable efficacy with better tolerability,"he said.
"Approval of this shorter course of PEG-INTRON and REBETOL combination therapy reflects the ongoing commitment of Schering-Plough to define optimal dose and treatment schedules to better meet the needs of hepatitis C patients,"said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute.
The Commission approval results in Marketing Authorization with unified labeling that is valid in the current EU 25 member states as well as in Iceland and Norway. PEG-INTRON and REBETOL combination therapy was previously approved in the EU for a 48-week course of therapy for all patients with genotype 1 who exhibit virological response at week 12.
Study Results
The approved labeling change for PEG-INTRON and REBETOL is based on results of a clinical study involving 235 patients with HCV genotype 1 and low viral load who received 24 weeks of combination therapy with PEG-INTRON (1.5 mcg/kg once weekly) and REBETOL (800 - 1,400 mg daily); only two patients weighing >105 kg received the 1,400 mg dose. In the study, 41 percent of patients (97/235) had undetectable plasma HCV-RNA levels at week 4 and week 24 of therapy. Patients in this subgroup achieved a 92 percent (89/97) rate of sustained virological response. The high SVR in this group of patients was identified in an interim analysis and prospectively confirmed.
Genotype 1 virus is the most common worldwide, the most difficult to treat successfully and accounts for about 70 percent of HCV infections among European patients overall, varying by geography. For patients with HCV genotypes 2 or 3, the EU labeling for PEG-INTRON recommends that all patients be treated for 24 weeks. Patients infected with HCV genotype 4 are considered harder to treat and generally 48 weeks of therapy is recommended. In the United States, PEG-INTRON is indicated in combination with REBETOL (800 mg daily) for 48 weeks.
About PEG-INTRON and REBETOL Combination Therapy
PEG-INTRON and REBETOL combination therapy for chronic hepatitis C was approved in the European Union in March 2001. The recommended dose in the EU for combination therapy is PEG-INTRON 1.5 mcg/kg once weekly plus REBETOL 800-1,200 mg daily, adjusted to body weight. PEG-INTRON had previously received centralized marketing authorization in the EU and is marketed as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C.
PEG-INTRON, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance between antiviral activity and elimination half-life. REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity.
Chronic hepatitis C is estimated to affect more than 10 million people in major world markets, including 5 million in Europe. It is a leading cause of chronic liver disease and one of the most common reasons for liver transplant in Europe.
Important Information Regarding U.S. Labeling for PEG-INTRON and REBETOL
WARNING:
Alpha interferons, including PEG-INTRON, 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 PEG-INTRON therapy.
Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. 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.
REBETOL and combination REBETOL/PEG-INTRON 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. REBETOL and combination REBETOL/PEG-INTRON 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 (at least two reliable forms) during treatment and during the 6-month post-treatment follow-up period. Significant teratogenic and/or embryocidal 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.
PEG-INTRON
There are no new adverse events specific to PEG-INTRON as compared to INTRON A (interferon alfa-2b, recombinant) for Injection, 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/REBETOL is contraindicated in patients with autoimmune hepatitis, decompensated liver disease, and in patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia).
The following serious or clinically significant adverse events have been reported at a frequency less than 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.
In the PEG-INTRON/REBETOL combination trial the incidence of serious adverse events was 17% in the PEG-INTRON/REBETOL groups compared to 14% in the INTRON A/REBETOL group. The incidence of severe adverse events in the PEG-INTRON/REBETOL combination therapy trial was 23% in the INTRON A/REBETOL group and 31-34% in the PEG-INTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42% of patients receiving PEG-INTRON (1.5 mcg/kg)/ REBETOL and in 34% of those receiving INTRON A/REBETOL.
REBETOL should not be used in patients with creatinine clearance less than 50 mL/min.
Schering-Plough Corporation is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company's Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: This press release contains "forward-looking statements"within the meaning of the Securities Litigation Reform Act of 1995, related to the market for PEG-INTRON and REBETOL combination therapy and the market for drugs to treat hepatitis C. Forward-looking statements relate to expectations or forecasts of future events and not to historical information. Schering-Plough does not assume the obligation to update any forward-looking statement. There are no guarantees about the market performance of PEG-INTRON and REBETOL combination therapy, Schering-Plough stock or Schering-Plough's business. Actual results may vary materially from Schering-Plough's forward-looking statements due to many factors and uncertainties, which include the market acceptance of PEG-INTRON and REBETOL combination therapy, trade buying patterns, the introduction and performance of competitive products in the market, legislation that may impact the pricing/availability of PEG-INTRON and REBETOL combination therapy and other uncertainties. For further details about these factors and other risks and uncertainties that may impact Schering-Plough's forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including the company's second quarter 2005 10-Q.
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