Food and Drug Administration approval of the immunosuppressant drug everolimus has been expanded to include prophylaxis of organ rejection in adults undergoing a liver transplant.
The approval, on Feb. 15, was announced by the manufacturer, Novartis. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, was first approved for prophylaxis of organ rejection in adults undergoing a kidney transplant in 2010, and is taken twice a day by mouth.
The approved indication states that in liver transplant recipients, everolimus is used in combination with the calcineurin inhibitor tacrolimus (at a reduced dose) and corticosteroids, and that it should be administered no earlier than 30 days post transplant. Safety and efficacy have not been established in pediatric patients, according to the prescribing information.
FDA approval was based on the 12-month results of a phase III, open-label international study of 719 liver transplant recipients (mean age, 54 years). At 12 months, the rate of the "efficacy failure" endpoint (defined as biopsy-proven acute rejection, graft loss, death, or loss to follow-up) was "comparable" between those patients treated with the reduced dose of everolimus, started 30 days after transplantation (9%), and the patients treated with the standard dose of tacrolimus, started 30 days after transplantation (13.6%), according to the Novartis statement and prescribing information. All patients were treated with corticosteroids.
Everolimus is the first mTOR inhibitor approved for liver transplant recipients, and is the first immunosuppressant approved by the FDA for use in liver transplant recipients in more than 10 years, according to Novartis.
Novartis markets everolimus in the United States as Zortress. It was approved in the European Union in the fourth quarter of 2012 for adult liver transplant recipients; it is marketed as Certican in Europe.
The new label is available here. Serious adverse events associated with everolimus should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.