New data from a fairly sizable, open-label follow-up trial, presented at the 2015 American Transplant Congress (ATC) in Philadelphia, showed a statistically significant 43% relative risk reduction of death or transplant failure in patients receiving the belatacept (Nulojix) FDA-approved dosing regimen.
While there’s been a marked improvement in short-term outcomes in kidney transplantation over the last 20 years, there remains a significant unmet need for treatments that improve long-term survival. New data from a fairly sizable, open-label follow-up trial, presented at the 2015 American Transplant Congress (ATC) in Philadelphia, showed a statistically significant 43% relative risk reduction of death or transplant failure in patients receiving the belatacept (Nulojix) FDA-approved dosing regimen over those receiving a cyclosporine regimen.
Nulojix is the first selective T-cell costimulation blocker indicated in combination with basiliximab induction, mycophenolate mofetil (MMF) and corticosteroids for the prophylaxis of organ rejection in adult Epstein-Barr Virus (EBV) seropositive patients receiving a kidney transplant.
The 7-year, long-term follow-up from a prospective, randomized phase 3 trial (BENEFIT) followed 666 renal transplant recipients of standard criteria deceased donor (SCD) and living donor kidneys in 3 cohorts. SCD kidneys were defined as organs from deceased donors with an anticipated cold ischemia time of less than 24 hours and not meeting the definition of extended criteria donor (ECD) organs. In the open-label, comparative, multicenter study study, Nulojix was compared with cyclosporine; 1 cohort received a less intensive dose of Nulojix (n=226), 1 received a more intensive dose of Nulojix (n=219), and 1 received cyclosporine (n=221). All patients also received basiliximab induction, MMF and corticosteroids. The trial excluded recipients undergoing first transplant with current panel reactive antibodies (PRA, a measure of pre-existing antibodies that may negatively impact the kidney transplant) ≥50% and recipients undergoing retransplantation with current PRA ≥30%; patients with HIV, hepatitis C or evidence of current hepatitis B infection, active tuberculosis, and those in whom intravenous access was difficult to obtain.
The study demonstrated a 43% relative risk reduction of death or graft loss (transplant failure) (hazard ratio=0.57, P=.0286), as well as improved kidney function, in patients receiving a less intensive (LI) or more intensive (MI) dose of Nulojix over cyclosporine. The LI group received the current FDA-approved dosing regimen of Nulojix. Specifically, at month 84, mean calculated glomerular filtration rate (cGFR, a measure of renal function) was 78 ml/min/1.73m2 for the LI dosing group and 51 ml/min/1.73m2 for the group receiving cyclosporine regimen (hazard ratio=0.57, P=.0286). Data also showed that there was a statistically significant survival benefit of 52% relative risk reduction of death or graft loss at 5 years post-transplant (hazard ratio=0.477, P=.0045). In the long-term follow-up (years 3-7) on BENEFIT participants, the safety profile of the Nulojix regimen was similar to the cyclosporine regimen.
In the long-term follow-up (years 3-7) of the BENEFIT study, the safety profile of Nulojix was similar to cyclosporine, with similar rates of serious adverse events across the treatment groups (69% among patients receiving the Nulojix regimen and 76% among patients receiving the cyclosporine regimen). The incidence rates (calculated as per 100-person years) were also similar among both groups for fungal infections (6.7 and 7.6, respectively), viral infections (14.2 and 15.7, respectively) and malignancies (1.7 and 2.6, respectively).
Dr Meier-Kriesche “We are still analyzing the 7-year BENEFIT study data and assessing the regulatory potential of these findings. The improvement seen in outcomes over cyclosporine, a current standard-of-care-class therapy, may help decision-makers when weighing the benefits of treatment options for long-term performance,” said Ulf Meier-Kriesche, MD, Worldwide Medical Lead, Nulojix, Bristol-Myers Squibb.
The study was sponsored by Bristol-Myers Squibb