The FDA ( Food and Drug Administration ) 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.
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.
Calcineurin inhibitors have been associated with injury to the kidneys and, when used in a combination-immunosuppressant regimen, increase the risk of infections and malignant tumors.
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.
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.
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.
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 ( greater than or equal to 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.
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. ( Xagena )
Source: Novartis, 2010