The European Commission approved Wyeth’s drug for adult patients with relapsed and/or refractory mantle cell lymphoma (MCL), called Torisel. This mTOR (mammalian target of rapamycin) inhibitor is indicated in the U.S. for the treatment of patients with advanced renal cell carcinoma (RCC).
Torisel won approval for RCC in the EU in November 2007 as a first-line treatment of patients who have at least three of six prognostic risk factors. These risk factors include less than one year from time of initial RCC diagnosis to randomization, Karnofsky performance status of 60 or 70, hemoglobin less than the lower limit of normal, corrected calcium of greater than 10 mg/dL, lactate dehydrogenase greater than 1.5 times the upper limit of normal, and more than one metastatic organ site.
The approval was based on results of a Phase III study that showed that patients treated with Torisel experienced a statistically significant improvement in median progression-free survival compared with single-agent therapy (4.8 months vs. 1.9 months). The most frequently occurring severe or life-threatening adverse events included thrombocytopenia, anemia, neutropenia, and asthenia.
Inhibition of mTOR in treated cancer cells blocked the translation of genes that regulate the cell cycle, according to Wyeth. In in vitro studies using renal cancer cell lines, Torisel inhibited the activity of mTOR and resulted in reduced levels of the hypoxia-inducible factors HIF-1 and HIF-2 alpha and the vascular endothelial growth factor.