Approval for Novartis' Zortress

Novartis has announced the US Food and Drug Administration (FDA) has approved Zortress (everolimus), its drug to prevent organ rejection in adult recipients of kidney transplants.

The drug, which comes in oral tablet form, has previously been available in more than 70 countries outside the US under the name Certican, with its first approval in 2003.

The US approval comes with a Risk Evaluation and Mitigation Strategy (REMS) – a document which the FDA has the authority to request from manufacturers to ensure the benefits of a treatment outweigh potential risks. This is used to guide patients and healthcare providers in using the treatment safely and managing possible side-effects.

Zortress was approved following the largest ever single phase III registration study conducted in kidney transplant recipients. The study found Zortress to prevent acute organ rejection and preserve kidney function while allowing, on average, 60 per cent lower doses of the calcineurin inhibitor (CNI), cyclosporine, than the control regimen treatment of mycophenolic acid (MPA) with full dose cyclosporine and corticosteroids.

CNIs are a typical treatment following an organ transplant, forming part of an immunosuppressive regimen to protect the transplanted organ from being rejected by the recipient's immune system. CNIs can have serious side-effects however, including damage to kidneys and, when used in a combination-immunosuppressant regimen, an increase in the risk of infections and malignant tumours.

Zortress was found to reduce these CNI-associated side effects while maintaining good efficacy. Adverse effects were still observed however, including constipation, hypertension and nausea, and therapeutic drug monitoring of Zortress and cyclosporine is recommended for all patients receiving these products.

"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 Dr Diane M Cibrik, 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."

Studies are currently ongoing to see the effect of everolimus following other organ transplants. The drugs effect on heart transplant patients is currently being observed in a phase III trial which will be used to support US filing, and a worldwide phase III liver transplant study is also in process.

Everolimus, the active ingredient in Zortress, is also available in the US under the brand name Afinitor as manufactured by Novartis. This is a different strength dosage of the drug and is used for the treatment of advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.