Afinitor® Approved In US As First Treatment For Patients With Advanced Kidney Cancer

Novartis announced today that Afinitor® (everolimus) tablets has been approved by the US Food and Drug Administration (FDA) for patients with advanced renal cell carcinoma (RCC) after failure of treatment with Sutent®(sunitinib)* or Nexavar® (sorafenib)**.

Prior to Afinitor, no other therapy has been studied in a Phase III trial in this patient population where there is an important unmet medical need[1]. Sutent and Nexavar are commonly used as initial treatments for advanced RCC[2]. The approval is based on data that showed Afinitor, when compared with placebo, more than doubled the time without tumor growth or death in patients with advanced kidney cancer (4.9 vs. 1.9 months) and reduced the risk of disease progression or death by 67% (hazard ratio=0.33 with 95% confidence interval 0.25 to 0.43; P<0.0001)[3]. Furthermore, additional data show that after 10 months of treatment with Afinitor, approximately 25% of patients still had no tumor growth[1], ***.

"This approval provides a new and useful tool for treating advanced renal cell cancer, representing an important step forward in managing this disease," said Robert J. Motzer, MD, attending physician, Memorial Sloan-Kettering Cancer Center, New York and principal investigator of the RECORD-1 trial, the basis for FDA approval of Afinitor. "New treatment options are vital to help us continue to offer patients with advanced kidney cancer new ways to battle their difficult-to-treat disease. Based on clinical trial data, this option should be considered when sunitinib or sorafenib fail."

In 2008, the FDA granted priority review status to Afinitor, previously known as RAD001, based on its potential to fill an unmet medical need for patients with advanced kidney cancer. Novartis has filed regulatory submissions in the European Union, Switzerland and Japan, as well as with other regulatory agencies globally[1].

Afinitor inhibits mTOR, a protein in the cancer cell that controls tumor cell division and blood vessel growth. Preclinical and clinical data have established the important role of mTOR in the development and progression of several types of tumors[1].

"With this approval, we can now offer patients a targeted therapy proven to fulfill an important unmet need in the treatment of advanced kidney cancer," said David Epstein, President and CEO, Novartis Oncology, Novartis Molecular Diagnostics. "We continue to study Afinitor in kidney cancer, and through a broad clinical program to explore its potential in many other tumor types."

About renal cell carcinoma
Renal cell carcinoma is often referred to as kidney cancer. Kidney cancer accounts for approximately 2% of all new cancers[4]. RCC is the most common type of kidney cancer, with occurrence rates rising steadily around the world due in part to smoking and obesity[5],[6]. It is estimated that about 54,000 new cases of RCC developed in the US in 2008 and more than 13,000 people died from the disease[7]. In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumor[8]. If left untreated, the tumor can spread to neighboring lymph nodes and eventually other organs[9].

RECORD-1 trial
The FDA regulatory filing for Afinitor was based on data from RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily), the largest Phase III clinical trial to study the effects of an oral mTOR inhibitor in advanced RCC patients whose cancer progressed despite prior treatment with sunitinib, sorafenib or both sequentially. In February 2008, based on a recommendation from an independent data monitoring committee, Novartis stopped the trial after interim results showed that patients receiving Afinitor experienced a significant delay in cancer progressing or death compared with patients receiving placebo[1].

This international, multi-center, randomized, double-blind trial involved 416 patients with advanced RCC whose cancer progressed despite prior treatment with sunitinib, sorafenib or both sequentially. In addition, prior therapy with bevacizumab, interferon alfa and interleukin-2 was allowed. Patients were randomized to receive Afinitor (10 mg) daily or placebo, in conjunction with best supportive care. The primary endpoint of the study was progression-free survival, which was assessed via a blinded independent, central radiological review[10].

About Afinitor
Afinitor is the first oral, daily therapy (5 mg and 10 mg tablets) to treat advanced kidney cancer after failure of treatment with sunitinib or sorafenib. In cancer cells, Afinitor continuously targets mTOR, a protein that acts as a central regulator of tumor cell division, blood vessel growth and cell metabolism. Afinitor is also being studied in multiple cancer types, including neuroendocrine, breast, gastric and hepatocellular carcinoma (HCC), as well as tuberous sclerosis complex (TSC) and non-Hodgkin's lymphoma[11].

The active ingredient in Afinitor is everolimus, which is available in different dosage strengths under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003. Certican is not approved for use in the US[1].

For more information on Afinitor, visit www.afinitor.com. US patients who may be eligible for financial assistance can learn about the AfiniTRAC(TM) reimbursement support program by contacting +1-888-5AfiniTRAC or visiting the website for Afinitor.

SOURCE: Novartis