Novartis Receives Approval for Organ Rejection Prevention Drug

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. The drug is to be given in combination with reduced doses of the calcineurin inhibitor (CNI) cyclosporine, as well as basiliximab and corticosteroids.

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.

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 percent 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.

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.

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.

The most common 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 five percent higher in patients given Zortress with reduced-dose cyclosporine than in those given mycophenolic acid and full-dose cyclosporine.

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.