Efficacy and safety of bleselumab in kidney transplant recipients: A phase 2, randomized, open‐label, noninferiority study

This study assessed the efficacy and safety of the anti‐CD40 monoclonal antibody bleselumab (ASKP1240) in de novo kidney transplant recipients over 36 months posttransplant. Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg per day immediate‐release tacrolimus [IR‐TAC]; target minimum blood concentration [Ctrough] 4‐11 ng/mL plus 1 g mycophenolate mofetil [MMF] twice daily) or bleselumab (200 mg on days 0/7/14/28/42/56/70/90, and monthly thereafter) plus either MMF or IR‐TAC (0.1 mg/kg per day; target Ctrough 4‐11 ng/mL days 0‐30, then 2‐5 ng/mL). All received basiliximab induction (20 mg pretransplant and on days 3‐5 posttransplant) and corticosteroids. One hundred thirty‐eight transplant recipients received ≥1 dose of study drug (SoC [n = 48]; bleselumab + MMF [n = 46]; bleselumab + IR‐TAC [n = 44]). For the primary endpoint (incidence of biopsy‐proven acute rejection [BPAR] at 6 months), bleselumab + IR‐TAC was noninferior to SoC (difference 2.8%; 95% confidence interval [CI] −8.1% to 13.8%), and bleselumab + MMF did not demonstrate noninferiority to SoC (difference 30.7%; 95% CI 15.2%‐46.2%). BPAR incidence slightly increased through month 36 in all groups, with bleselumab + IR‐TAC continuing to demonstrate noninferiority to SoC. Bleselumab had a favorable benefit–risk ratio. Most treatment‐emergent adverse events were as expected for kidney transplant recipients (ClinicalTrials.gov NCT01780844). In this phase 2a, randomized, open‐label study in kidney transplant recipients, bleselumab (a nondepleting, fully human, anti‐CD40 monoclonal antibody) + immediate‐release tacrolimus demonstrates noninferiority, but bleselumab + mycophenolate mofetil does not, versus the standard of care (immediate‐release tacrolimus + mycophenolate mofetil) for the prevention of biopsy‐proven acute rejection, but both bleselumab groups demonstrate a favorable benefit–risk ratio, with safety profiles that are as expected for this patient population. See the related article by Vincenti et al on page 172.