Basel, April 22, 2010 - The US Food and Drug Administration (FDA) has approved Zortress (everolimus) oral tablets for the prevention of organ rejection of kidney transplants in adult patients at low-to-moderate immunologic risk. Zortress is to be given in combination with reduced doses of the calcineurin inhibitor (CNI) cyclosporine, as well as basiliximab and corticosteroids[4].

Under the brand name Certican®, everolimus is already an established part of the immunosuppressive regimen for transplant patients in more than 70 countries outside the US.

"For patients who require a kidney transplant, the limited availability of organs underscores the urgent need for effective medicines that can help protect the survival of the transplanted organ for the patient," said David Epstein, Division Head of Novartis Pharmaceuticals. "Our commitment to transplant patients exceeds 25 years, and Zortress is the latest addition to our growing portfolio. This includes five medications that enable clinicians to provide various treatment options to help manage their individual kidney transplant patients."

FDA approval of Zortress was based on results from the largest single Phase III registration study ever conducted in kidney transplant recipients. In the study, Zortress prevented acute organ rejection and preserved kidney function while allowing, on average, 60% lower doses of the CNI cyclosporine to be used compared with the control regimen of mycophenolic acid (MPA) with full dose cyclosporine and corticosteroids. Use of Zortress led to a reduction in CNI-associated side effects while maintaining good efficacy[1].

Calcineurin inhibitors, which are part of the typical immunosuppressive regimen, have been associated with injury to the kidneys and, when used in a combination-immunosuppressant regimen, increase the risk of infections and malignant tumors[3].

Following transplantation, immunosuppressive medicines are required to protect the transplanted organ from being rejected by the recipient's immune system. Antigen-activated T cells play a key role in transplant rejection by recognizing foreign substances and multiplying in an attempt to protect the body. Zortress acts as an immunosuppressant by binding to a protein called mammalian target of rapamycin (mTOR) and preventing the proliferation of these antigen-activated T cells[3].

"Transplant recipients require lifelong immunosuppression, so there is a critical need for treatment regimens that protect the transplanted kidney, and also reduce the side effects and infections associated with calcineurin inhibitors," said Diane M. Cibrik, MD, Associate Professor of Medicine and Medical Director of Transplant Clinical Research Trials at the University of Michigan. "Based on its different mode of action, Zortress offers the ability to reduce calcineurin inhibitors, and may help to address this unmet need."

In 2009, an estimated 16,800 kidney transplants were performed in the US, and an estimated 4,500 kidney transplant candidates died while awaiting organ donation. As of March 2010, there were more than 83,000 patients awaiting kidney transplantation in the US[5].

Organ survival rates one year after a successful kidney transplant range from 89% when the organ comes from a deceased donor to 95% when the donor is living. However, percentages drop five years after transplantation with survival rates of approximately 67% and 80% respectively[5].

Zortress has been approved in the US with a Risk Evaluation and Mitigation Strategy (REMS) to help guide patients and healthcare providers on the safe use and risks of Zortress following kidney transplantation. The approved REMS includes a medication guide, a communications plan and a timetable for submission of assessments.

The most common (≥ 20%) adverse events observed with Zortress are peripheral edema, constipation, hypertension, nausea, anemia, urinary tract infection and hyperlipidemia. Events such as peripheral edema, dyslipidemia and hyperlipidemia were at least 5% higher in patients given Zortress with reduced-dose cyclosporine than in those given mycophenolic acid and full-dose cyclosporine[4].

Increased susceptibility to infection and possible development of malignancies may result from immunosuppression. Potential serious adverse events associated with Zortress include lymphoma and other malignancies, as well as serious infections. Increased risk of kidney graft thrombosis has also been reported with Zortress. Therapeutic drug monitoring of everolimus and cyclosporine is recommended for all patients receiving these products.

The active ingredient in Zortress is everolimus, which was first approved in 2003 under the brand name Certican and is used for kidney and heart transplantation in more than 70 countries outside the US. A Phase III study using everolimus in heart transplant is under way to support US filing, and a worldwide Phase III liver transplant study is ongoing.

Everolimus is also available in different dosage strengths under the brand name Afinitor® for the treatment of advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Afinitor was approved in the US in 2009.

About Novartis Transplant Medicines

As a company committed to research, development and the marketing of therapies that improve health, ease suffering and enhance patients' quality of life, Novartis is a leader in transplantation and immunology. With the discovery and introduction of cyclosporine more than 25 years ago, Novartis has contributed to improving treatment options for transplant patients and now has the broadest portfolio of immunosuppressants on the market.