FDA approves first drug in over a decade for prevention of organ rejection

FDA has approved everolimus (Zortress, Novartis) for the prophylaxis of organ rejection in adult patients receiving a liver transplant.

Everolimus is the first mammalian target of rapamycin (mTOR  inhibitor) approved for use following liver transplantation. It is also the first immunosuppressant approved by FDA in more than a decade for use following liver transplantation.

"The approval of [everolimus] serves as another breakthrough in the number of available treatment options for individuals following liver transplantation," said Abimbola Farinde, PharmD, MS, clinical staff pharmacist at Clear Lake Regional Medical Center, in Webster, Texas. “The dual FDA approval of [everolimus] for liver transplantation and as a immunosuppressant will allow for the increased utilization of this agent as well as providing another therapeutic options for providers to choose from when treating patients.”

The approval was based on the largest liver transplant study to date, which showed that everolimus plus reduced tacrolimus led to comparable efficacy and 10 mL/min higher renal function as measured by estimated glomerular filtration rate (eGFR) for everolimus compared to standard tacrolimus at 12 months.

"While prevention of acute organ rejection is a key priority for physicians following liver transplantation, managing other health risks, including impaired renal function associated with calcineurin inhibitor treatment, is also critical," said John Fung, MD, PhD, director, Transplantation Center, Cleveland Clinic Foundation, Cleveland, Ohio, in a press release. "With the approval of Zortress, the first mTOR inhibitor approved for liver transplant patients, we have a new treatment option that has the potential to address the unmet medical need for maintaining renal function without compromising acute rejection rates-and that's important for patients and physicians."

The FDA approval was based on 12-month results from a phase 3, multicenter, open-label, randomized, controlled study conducted in 719 liver transplant patients starting 30 days post-transplant. In liver transplantation, everolimus is to be administered no earlier than 30 days post-transplant concurrently in combination with reduced doses of tacrolimus and with corticosteroids. Therapeutic drug monitoring is recommended. In the study, during the first 30 days after transplant and prior to randomization, patients received tacrolimus and corticosteroids, with or without mycophenolate mofetil. No induction antibody was administered.