Approval for Temodar (temozolomide) capsules for newly diagnosed glioblastoma multiforme

Schering-Plough today reported that the U.S. Food and Drug Administration (FDA) has granted approval for Temodar (temozolomide) Capsules for use in combination with radiotherapy for the treatment of adult patients with newly diagnosed glioblastoma multiforme (GBM), a form of malignant brain cancer.

The approval was based on data that demonstrated a significant overall survival benefit in patients who were treated with Temodar in combination with radiotherapy. Concurrent with the approval for newly diagnosed GBM, Temodar also received full approval for the treatment of adult patients with refractory anaplastic astrocytoma (AA), another form of brain tumor. Temodar received accelerated approval for AA in 1999 and is currently marketed for this indication in the United States.

"Temodar represents an important component for patients and physicians in the fight against GBM and validates the real benefits of chemotherapy in treating this disease," said Dr. Henry Friedman, co-director, Clinical Neuro-Oncology Program, The Brain Tumor Center at Duke. "After 26 years of practicing neuro-oncology, I view Temodar as a significant advancement in battling GBM."

The full approval of Temodar follows a priority review of the supplemental new drug application containing the GBM data that was submitted in September 2004. FDA grants priority review status to drugs that, if approved, would address unmet medical needs and represent significant advances over existing treatments.

"We are very pleased with today's FDA action and what it means for patients with GBM, the most serious and aggressive type of malignant brain tumor," said Robert J. Spiegel, M.D., chief medical officer and senior vice president of medical affairs, Schering-Plough Research Institute. "This approval represents a significant advance in the treatment of brain cancer, a disease for which few effective treatments exist."

The approval of Temodar for newly diagnosed GBM was based on efficacy and safety data from a landmark Phase III study conducted by the European Organisation for Research and Treatment of Cancer (EORTC)(1) in patients with newly diagnosed GBM. These data were published in the March 10, 2005 edition of the New England Journal of Medicine.(2) In this multicenter trial of 573 patients, significant improvements in overall survival were observed in patients who were treated with Temodar in combination with radiotherapy. Myelosuppression was the dose-limiting adverse event. The most common adverse events across the cumulative Temodar experience were alopecia, nausea, vomiting, anorexia, headache, and constipation. Forty-nine percent of patients treated with Temodar reported one or more severe or life-threatening events, most commonly fatigue (13%), convulsions (6%), headache (5%) and thrombocytopenia (5%). There may be a higher occurrence of opportunistic infections such as pneumocystis carinii pneumonia (PCP) when Temodar is administered during a longer dosing regimen. However, all patients receiving Temodar, particularly patients receiving steroids, should be observed closely for the development of PCP regardless of the regimen.

Under the full approval, Temodar is now indicated for use in adult patients with newly diagnosed GBM concomitantly with radiotherapy and then as maintenance treatment after the patient has completed radiotherapy. In patients with refractory AA, Temodar is indicated for use in adult patients who have experienced disease progression on a drug regimen containing nitrosurea and procarbazine.

Schering-Plough has filed an application with the European Medicines Agency (EMEA) seeking approval of a similar indication for first-line GBM. In the European Union, temozolomide is marketed as TEMODAL and is currently indicated for the treatment of patients with malignant glioma, such as GBM or AA, showing recurrence or progression after standard therapy.