Novartis announced two-year results from the largest Phase 3 study ever in liver transplantation that showed RAD001 (everolimus) with reduced exposure tacrolimus provided comparable efficacy and better renal function maintained from month one to 24. The trial evaluated the introduction of RAD001 with reduced exposure tacrolimus administered twice-daily starting one month after liver transplantation versus standard-exposure tacrolimus. In the US, RAD001 is an investigational agent for the prevention of organ rejection in adult patients receiving a liver transplant.
“Novartis has a longstanding commitment to the transplant community and to research into potential treatment options to help improve patient outcomes,” said Tim Wright, Global Head of Development, Novartis Pharma. “The promising renal function results seen in this study represent yet another potential advance for patients and build upon the recent approval of Certican for adult liver transplant patients by the European Health Authorities.”
The data were presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, MA.
“These results showed that treatment with RAD001 with reduced tacrolimus led to a clinically relevant retention of renal function compared to standard tacrolimus, with no compromise in rejection,” said John Fung, MD, PhD, Director, Transplantation Center, Cleveland Clinic Foundation, Cleveland, OH. “The two-year results suggest that a treatment regimen of RAD001 with reduced tacrolimus is not only possible, but also sustainable, and that’s exciting news for patients and their healthcare providers who are concerned about the impact of CNIs on renal function.”
A large, separate registry study of nearly 70,000 patients who received a non-renal solid organ transplant between 1990 and 2000 showed that the incidence of chronic renal failure was greater in liver transplant recipients than in recipients of all other solid organ transplants, except intestinal transplants. Calcineurin inhibitors (CNIs), such as tacrolimus, are part of the standard-of-care treatment regimen for immunosuppression in liver transplantation, but they can contribute to complications, including impaired renal function. RAD001 works by binding to a protein called mammalian target of rapamycin (mTOR), and acts synergistically with CNIs, offering an opportunity to lower CNI exposure.
In October 2012, European Health Authorities approved Certican (RAD001/everolimus) for the prophylaxis of organ rejection in adult patients receiving a liver transplant. In the US, RAD001 is an investigational agent for the prevention of organ rejection in adult patients receiving a liver transplant and a decision by the US Food and Drug Administration is expected by the end of 2012.
Date: November 12, 2012