Study Design Overview

The clinical data for NULOJIX^® are based on 2 trials: the BENEFIT study and BENEFIT-EXT study. The studies were phase 3, randomized, open-label, active-controlled, parallel-group, multicenter, 3-year trials comparing the efficacy and safety of NULOJIX to cyclosporine (CsA) in adults.^1-3

BENEFIT STUDY
Participants received a de novo kidney allograft from a living donor or a deceased standard criteria donor (SCD) with an anticipated cold ischemic time (CIT) of <24 hours (N=666).^1,2

BENEFIT-EXT STUDY
Participants received a de novo kidney allograft from a deceased extended criteria donor (ECD*) (N=543).^1,3

Dosing regimen^1-3

• All treatment groups also received basiliximab induction, MMF, and corticosteroids
• NULOJIX^† (BENEFIT study, n=226; BENEFIT-EXT study, n=175): 10 mg/kg on Day 1 (day of transplantation prior to implantation), Day 5 (~96 hours after Day 1 dose), and end of Weeks 2, 4, 8, and 12. Starting at end of Week 16,
  5 mg/kg every 4 weeks (plus or minus 3 days). Higher than recommended doses and/or more frequent dosing of NULOJIX are not recommended due to more efficacy failures; increased risk of PTLD, predominantly involving the CNS; progressive multifocal leukoencephalopathy (PML), often a rapidly progressive and fatal opportunistic infection; and serious CNS infections^‡
• Cyclosporine (BENEFIT study, n=221; BENEFIT-EXT study, n=184): 4-10 mg/kg then adjusted to serum levels 150-300 ng/mL within the first month, then 100-250 ng/mL within Months 2-12

Endpoints^1-3

Study endpoints are the same for BENEFIT and BENEFIT-EXT studies:

• Efficacy failure, defined as a composite of
  • Biopsy-proven acute rejection (BPAR)^§
  • Graft loss
  • Death
  • Lost to follow-up
• Composite patient and graft survival
• Renal function assessed as mean calculated glomerular filtration rate (cGFR)^||
• Cardiovascular/metabolic parameters
  • Hypertension, mean blood pressure
  • Dyslipidemia, mean change in serum lipids
  • Medication used for hypertension
  • Incidence of new-onset diabetes after transplantation (NODAT)^¶

^*ECD kidney defined as deceased donor organ with at least 1 of the following: donor age ≥60 years; donor age ≥50 years and other comorbidities (≥2 of the following: stroke, hypertension, serum creatinine >1.5 mg/dL); donation after cardiac death; anticipated cold ischemia time (CIT) ≥24 hours.

^†Dose based on actual body weight at time of transplant unless there was >10% change.

^‡A NULOJIX regimen with higher cumulative doses and more frequent dosing than the recommended dosage regimen was also studied (N=219). Study results for this arm are not reported here.

^§Histologically confirmed acute rejection by a central pathologist on a biopsy done for any reason, whether or not accompanied by clinical signs of rejection.

^||GFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.

^¶NODAT: Defined as use of an antidiabetic agent for ≥30 days or ≥2 fasting plasma glucose values ≥126 mg/dL (7.0 mmol/L) post-transplantation.

SELECTED IMPORTANT SAFETY INFORMATION

Post-Transplant Lymphoproliferative Disorder (PTLD)

• NULOJIX patients are at increased risk for developing PTLD, predominantly involving the central nervous system (CNS)
• Recipients without immunity to EBV (ie, seronegative) are at particularly increased risk; therefore, NULOJIX is contraindicated in transplant recipients who are EBV seronegative or with unknown serostatus
• Monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms
• As the total burden of immunosuppression is a risk factor for PTLD, higher than recommended doses or more frequent dosing of NULOJIX or concomitant immunosuppressive agents are not recommended
• Other known risk factors for PTLD include cytomegalovirus (CMV) infection and T cell-depleting therapy
  • CMV prophylaxis is recommended for at least 3 months after transplantation
  • Use T cell-depleting therapy to treat acute rejection cautiously
• Patients who are EBV seropositive and CMV seronegative may be at increased risk of PTLD
  • Since CMV seronegative patients are at increased risk for CMV disease (a known risk factor for PTLD), the clinical significance of CMV serology for PTLD remains to be determined; however, these findings should be considered when prescribing NULOJIX

References

1. NULOJIX [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company.
2. Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010;10(3):535-546.
3. Durrbach A, Pestana JM, Pearson T, et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant. 2010;10(3):547-557.

View Efficacy Data  View Renal Function Data