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KENILWORTH, N.J., Dec. 8 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion recommending approval of the intravenous (IV) formulation of TEMODAL(R) (temozolomide) as an alternative to the already approved oral form of temozolomide in the EU. The CHMP also has issued a positive opinion recommending approval of a sachet packaging presentation for TEMODAL Capsules. This new presentation was created to provide greater patient convenience and flexibility.
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TEMODAL Capsules are a chemotherapy agent approved in the EU for treatment of patients with newly diagnosed glioblastoma multiforme (GBM) concomitantly with radiotherapy and subsequently as monotherapy, and for patients with malignant gliomas, such as GBM or anaplastic astrocytoma (AA), showing recurrence or progression after standard therapy. The CHMP recommendation serves as the basis for a European Commission approval of the IV formulation of TEMODAL and the sachet presentation of TEMODAL Capsules. In the US, temozolomide, marketed as TEMODAR(R) Capsules, is approved for the treatment of adult patients with newly diagnosed GBM concomitantly with radiotherapy and then as maintenance treatment, as well as for refractory AA, ie, patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.
"TEMODAL is a well recognized, effective treatment for patients in Europe with malignant gliomas, but is only available orally. Upon approval, the IV formulation of TEMODAL can provide patients in the EU with an important alternative route of administration, and the sachet presentation can offer flexibility and a more convenient form of packaging," said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute. "These two new options demonstrate Schering-Plough's commitment to providing effective treatments in a variety of presentations for specific patient needs and for patient convenience."
About temozolomide
TEMODAL (temozolomide), a cytotoxic agent, is currently approved in oral form as 5mg, 20mg, 100mg, 140mg, 180mg and 250mg capsules in Europe. Cytotoxic agents are designed to impact the replication of cells that divide rapidly, such as those in tumors. TEMODAL was initially approved in the European Union (EU) in 1999 for the treatment of patients with malignant glioma, such as GBM or AA, showing recurrence or progression after standard therapy. In June 2005, TEMODAL received marketing approval in the EU for the treatment of patients with newly diagnosed GBM concomitantly with radiotherapy and subsequently as monotherapy treatment. The TEMODAL IV formulation reviewed by the CHMP was developed for cancer patients who are unable to take TEMODAL Capsules and has shown bioequivalence to the oral product. The sachet packaging presentation for TEMODAL Capsules was created to provide greater patient convenience and flexibility.
Schering-Plough has received a Complete Response Letter from the U.S. Food and Drug Administration for the TEMODAR IV formulation and is working with the agency to address outstanding questions.
TEMODAR capsules (temozolomide) received accelerated approval from the U.S. Food and Drug Administration (FDA) for adult patients with refractory AA in 1999 and full approval in March 2005 for refractory AA, ie, patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine, and for the treatment of newly diagnosed GBM concomitantly with radiotherapy and then as maintenance treatment.
About Malignant Gliomas
The worldwide incidence rate of primary malignant brain and central nervous system tumors, using the world standard population, is 3.7 per 100,000 person in males and 2.6 per 100,000 person in females(1). The most common type of primary malignant brain tumors are gliomas, with AA and GBM being the most common and among the most serious types.
Important Information Regarding EU Labeling for TEMODAL
Full prescribing information for TEMODAL can be found at http://www.emea.europa.eu/humandocs/Humans/EPAR/temodal/temodal.htm
Important Information Regarding US Labeling for TEMODAR
TEMODAR Capsules are contraindicated in patients who have a history of hypersensitivity to any of its components, or to DTIC.
Patients treated with TEMODAR Capsules may experience myelosuppression including prolonged pancytopenia, which may result in aplastic anemia, which in some cases has resulted in a fatal outcome. In some cases, exposure to concomitant medications associated with aplastic anemia including carbamazepine, phenytoin, and sulfamethoxazole/trimethoprim complicates assessment. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression. Cases of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, have also been observed.
TEMODAR may cause fetal harm when administered to a pregnant woman. Nursing should be discontinued in women taking TEMODAR.
Prophylaxis against Pneumocystis carinii pneumonia is required for all patients receiving concomitant TEMODAR and radiotherapy for the 42-day regimen. There may be a higher occurrence of PCP when temozolomide is administered during a longer dosing regimen. However, all patients receiving temozolomide, particularly patients receiving steroids, should be observed closely for the development of PCP regardless of the regimen.
Caution should be exercised when administered to those with severe hepatic or renal impairment.
TEMODAR Capsules should not be opened or chewed. If capsules are accidentally opened or damaged, rigorous precautions should be taken with the capsule contents to avoid inhalation or contact with the skin or mucous membranes.
The effectiveness of TEMODAR in children has not been established.
In newly diagnosed patients with GBM, the adverse event profile was similar in patients <65 years of age and those greater than or equal to 65 years.
In newly diagnosed GBM, the most common adverse events in clinical
studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were alopecia 69%, 55%; fatigue 54%, 61%; nausea 36%, 49%; vomiting 20%, 29%; anorexia 19%, 27%; headache 19%, 23%; constipation 18%, 22%; with the following important adverse events also reported: convulsions 6%, 11% and thrombocytopenia 4%; 8%.
Of these adverse events, those grade greater than or equal to 3 in clinical studies in the Concomitant Phase (Radiotherapy + TEMODAR) and the Maintenance Phase (TEMODAR alone), respectively, were fatigue 7%, 9% nausea; 1%, 1%; vomiting <1%, 2%; anorexia 1%, 1%; headache 2%, 4%; constipation 1%, 0%; convulsions 3%, 3%; thrombocytopenia 3%, 4%.
In the newly diagnosed GBM population, when laboratory abnormalities and adverse events were combined, Grade 3 or 4 neutropenia occurred in 8% and Grade 3 or 4 platelet abnormalities including thrombocytopenic events occurred in 14% of patients treated with temozolomide.
Most common adverse reactions in the trial in AA patients Grade 3/4 and overall, respectively were: nausea 10%, 53%; vomiting 6%, 42%; headache 6%, 41%; fatigue 4%, 34%; constipation 1%, 33%; convulsions 5%, 23%; with the following important adverse events also reported: hemiparesis 6%, 18%; asthenia 6%, 13%;
Adverse hematologic effects (Grade 3 to 4) in the AA trial in adults were lymphopenia (55%); platelets (19%); neutrophils (14%) and hemoglobin (4%).
7% and 9.5% of patients over age 70 experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. For patients less than or equal to age 70, 7% and 5.5% experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively.
Full prescribing information for TEMODAR can be found at http://www.spfiles.com/pitemodar.pdf
About Schering-Plough
Schering-Plough is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription, animal health and consumer health care products. Schering-Plough's vision is to "Earn Trust, Every Day" with the doctors, patients, customers and other stakeholders served by its colleagues around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH 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 relating to TEMODAL and the potential market for TEMODAL.
Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward-looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details about these and other factors that may impact the forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Part II, Item 1A. "Risk Factors" in the third quarter 2008 10-Q, filed October 29, 2008.
Endnotes
(1)Central Brain Tumor Registry of the US, via http://www.abta.org/siteFiles/SitePages/83160A946479BA7251511169BCA46C90.pdf
SOURCE Schering-Plough Corporation
