Wyeth was all smiles yesterday after US drug regulators gave its first in class anticancer drug Torisel (temsirolimus) the thumbs up for patients with advanced kidney cancer. The targeted mTOR (mammalian target of rapamycin) inhibitor is the first targeted renal cancer therapy proven to extend median overall survival versus standard therapy with interferon-alpha in this patient population.
Renal cell carcinoma accounts for approximately 85% of kidney cancers. The American Cancer Society estimates that 51,190 new cases of kidney cancer will be diagnosed this year, and more than 40% of these patients are initially diagnosed with advanced disease. The disease is very difficult to treat and Torisel is the first drug to demonstrate a significant increase in overall survival in this most aggressive form of the disease.
In a Phase III study involving almost 630 patients with advanced kidney cancer and a poor prognosis, who had no received any prior therapy, Torisel increased median survival by almost 50% versus interferon-alpha (10.9 months vs 7.3 months). Progression-free survival was also improved significantly, rising from 3.1 months in patients receiving interferon-alpha to 5.5 months in the group given Torisel. A third group receiving a combination of the two agents showed no improvement in overall survival.
The most common adverse reactions, occurring in at least 30% of Torisel-treated patients, were rash, fatigue, mouth sores, nausea, edema, and loss of appetite. The most common laboratory abnormalities were high blood sugar, elevated blood lipids and triglycerides, elevated liver and kidney blood tests, and low red cell, white cell, and platelet counts.
Torisel works by inhibiting a key protein responsible for regulating the proliferation, growth and survival of cells called mTOR (mammalian target of rapamycin) kinase.
Launch scheduled for July
Wyeth hopes to launch Torisel in July but has also committed to two post-marketing requests for completed study reports and data sets: one on a thorough QT prolongation study and one on an ongoing hepatic impairment study. In addition, Torisel is also being explored in a Phase III study in mantle cell lymphoma, which is an aggressive type of B-cell non-Hodgkin's lymphoma, as well as several additional studies in RCC.
"We have made significant advances in the battle against kidney cancer,” said Steven Galson, director of the FDA’s Center for Drug Evaluation and Research. "Torisel is the third drug approved for this indication in the past 18 months, and one that shows an increased time in survival for some patients."
The approval of Torisel follows the December 2005 approval of Nexavar (sorafenib), which was based on a delay in progression of disease. In January 2006, Sutent (sunitinib) received accelerated approval based on durable response rate, or tumour size reduction, and was later demonstrated to delay tumour progression.