KENILWORTH, N.J., Dec. 10 /PRNewswire-FirstCall/ -- Schering-Plough Corporation today announced that PEG-INTRON(R) (peginterferon alfa-2b) Powder for Injection is now available in Japan for use in combination with REBETOL(R) (ribavirin) Capsules for the treatment of chronic hepatitis C. PEG-INTRON and REBETOL combination therapy, marketed by Schering-Plough K.K., the company's subsidiary in Japan, is the first and only pegylated interferon- based combination therapy available in Japan. An estimated 1 to 2 million Japanese are chronically infected with hepatitis C.
PEG-INTRON on Oct. 22 received marketing approval in Japan from the Ministry of Health, Labor and Welfare (MHLW) following a priority review. The product became available on Dec. 8 upon National Health Insurance Reimbursement price listing.
In Japan, PEG-INTRON is indicated in patients chronically infected with hepatitis C virus (HCV) genotype 1 (genotype 1a or 1b) and high viral load. HCV genotype 1 is considered the most difficult-to-treat form of hepatitis C and is the most common form in Japan, accounting for approximately 60 percent of all HCV infections there.
PEG-INTRON is administered once weekly in combination with REBETOL daily for 48 weeks. Importantly, PEG-INTRON is the only peginterferon product approved in Japan for which a blood test is not required before every injection.
In the Japanese clinical study supporting the approval, 48 weeks of PEG- INTRON and REBETOL combination therapy achieved a sustained virologic response (SVR)(1) rate of 48% in patients with HCV genotype 1 and high viral loads. An SVR rate of 63 percent was achieved with PEG-INTRON and REBETOL in the portion of these patients who had relapsed following previous interferon treatment.
Hepatitis C is the leading cause in Japan of chronic liver disease, cirrhosis, and hepatocellular carcinoma, which is associated with more than 30,000 deaths there annually. Hepatitis C is the most common reason for liver transplant in major world markets, including Japan, according to the World Health Organization (WHO).
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. PEG-INTRON is a longer- acting form of INTRON(R) A (interferon alfa-2b, recombinant) Injection.
REBETOL is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity. Schering-Plough K.K. currently markets REBETOL in Japan for use in combination with INTRON A for chronic hepatitis C.
In the United States, 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.
Important Safety Information from the U.S. PEG-INTRON Label
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.
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.
All patients receiving INTRON A therapy experienced mild-to-moderate side effects. Some patients experienced more severe side effects, including neutropenia, fatigue, myalgia, headache, fever, chills and increased SGOT. Other frequently occurring side effects were nausea, vomiting, depression, alopecia, diarrhea and thrombocytopenia. DEPRESSION AND SUICIDAL BEHAVIOR, INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS, AND COMPLETED SUICIDES, HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA INTERFERONS, INCLUDING INTRON A THERAPY.
Schering-Plough K.K., based in Osaka, is a wholly owned subsidiary of Schering-Plough Corporation, 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 is based in Kenilworth, N.J., USA, and its Web site is http://www.schering-plough.com/.
DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking" statements within the meaning of the Securities Litigation Reform Act of 1995, including statements concerning the availability of PEG- INTRON in Japan, the market for drugs to treat hepatitis C in Japan and Schering-Plough's products. Forward-looking statements relate to expectations or forecasts of future events and use words such as "may" and "will." Actual results may vary from the forward-looking statements, and there are no guarantees about the performance of Schering-Plough stock or Schering-Plough's business. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ from Schering-Plough's forward-looking statements. These factors include market acceptance of new products, product availability, current and future branded, generic and OTC competition, and trade buying patters. For further details and a discussion of these and factors that may impact Schering- Plough's forward-looking statements, see the company's past and future Securities and Exchange Commission filings, including the company's 2004 third quarter 10-Q and future SEC filings.
(1) SVR is defined as the sustained undetectability of the hepatitis C
virus for six months following therapy.