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Brain
CHMP Issues Positive Opinion for First-line Use of Temozolomide in the treatment of Glioblastoma Multiforme
By Schering-Plough Corporation, Apr 24, 2005 - 8:21:38 AM

Schering-Plough Corporation (NYSE: SGP - News) today reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has issued a positive opinion recommending approval of TEMODAL® (temozolomide) Capsules for first-line use in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM), the most common form of brain cancer. The CHMP recommendation serves as the basis for a European Commission approval.

TEMODAL is currently approved in the European Union (EU) for the treatment of patients with malignant glioma such as GBM or anaplastic astrocytoma, showing recurrence or progression after standard therapy.

Schering-Plough received full approval of temozolomide (TEMODAR®) from the U.S. Food and Drug Administration (FDA) on March 16, 2005 for the treatment of adult patients with newly diagnosed GBM when administered in combination with radiotherapy and then as maintenance therapy.

A Commission approval would result in centralised Marketing Authorization with unified labeling throughout the EU, covering the use of TEMODAL for the treatment of patients with newly diagnosed GBM concomitantly with radiotherapy followed by up to 6 cycles of temozolomide monotherapy.

The new labeling will be in addition to the currently approved indication, and will be valid in the current 25 EU Member States as well as in Iceland and Norway, once approval is granted by the European Commission.

The positive opinion recommending the labeling expansion for TEMODAL is based largely on efficacy and safety data from a landmark Phase III study conducted by the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC). These data were published in the March 10, 2005 edition of the New England Journal of Medicine. In this multicenter trial of 573 patients with newly diagnosed GBM, significant improvement in overall survival was observed in patients who were treated with TEMODAL in combination with radiotherapy compared with those treated with radiotherapy alone.

In this study, more than twice as many patients (26 percent) in the TEMODAL group survived two years, compared with 10 percent of those who received radiotherapy alone. Median survival in the TEMODAL group was also significantly better (14.6 vs. 12.1 months) compared to the radiotherapy only group. TEMODAL treatment was generally well tolerated; the most commonly observed adverse events (greater than 10%) in patients receiving TEMODAL in combination with radiotherapy followed by TEMODAL monotherapy included decreased appetite, headache, constipation, nausea, vomiting, hair loss, rash, convulsions and fatigue.

Low white blood cells and low platelets, which are known dose-limiting toxicities for most cytotoxic agents, including TEMODAL, were observed. When laboratory abnormalities and adverse events were combined across concomitant and monotherapy treatment phases, Grade 3 or Grade 4 neutrophil abnormalities including neutropenic events were observed in 8% of the patients.

Grade 3 or Grade 4 thrombocyte abnormalities, including thrombocytopenic events were observed in 14% of the patients who received TEMODAL.

Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute, explained that the CHMP approval recommendation reflects the findings of this important, independent study. "This landmark EORTC study clearly demonstrated that TEMODAL offers significant improvement in prognosis for newly diagnosed GBM patients compared with standard treatment, and is safe and well tolerated. This represents an important advance in the treatment of GBM, one of the most serious and aggressive types of malignant brain tumor."

About Temozolomide

Temozolomide is an oral, cytotoxic alkylating agent. Cytotoxic agents are designed to prevent the replication of cells that divide rapidly, including those in tumors. The development of temozolomide for expanded indications is consistent with Schering-Plough's strategy to broaden its oncology portfolio and is in line with its plans to build strength in its global franchises through both internal research and external collaborations and licensing opportunities.

Important Information Regarding U.S. Labeling for TEMODAR with Newly Diagnosed GBM

Patients treated with TEMODAR Capsules may experience myelosuppression.

Grade 3/4 neutropenia occurred in 8% and Grade 3/4 thrombocytopenia in 14% of patients treated with temozolomide.

Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression.

TEMODAR Capsules are contraindicated in patients who have a history of hypersensitivity to any of its components, or to DTIC.

Caution should be exercised when administered to those with severe hepatic or renal impairment.

TEMODAR may cause fetal harm when administered to a pregnant woman. Nursing should be discontinued in women receiving TEMODAR.

The effectiveness of TEMODAR in children has not been established.

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.

Prophylaxis against Pneumocystis carinii pneumonia (PCP) is required in all patients receiving TEMODAR in combination with radiotherapy for the 42-day regimen. There may be a higher occurrence of PCP when temozolomide is administered during a longer dosing regimen. All patients receiving TEMODAR, particularly patients receiving steroids, should be observed closely for the development of PCP regardless of the regimen.

As noted in the U.S. package insert, during the concomitant phase (TEMODAR + radiotherapy), adverse events including thrombocytopenia, nausea, vomiting, loss of appetite and constipation, were more frequent in the TEMODAR + radiotherapy arm versus the radiotherapy arm alone. The incidence of other adverse events were comparable in the two arms.

The most common adverse events across the cumulative TEMODAR experience were hair loss, nausea, vomiting, decrease in appetite, headache and constipation.

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