Purpose: To assess the potential of CFZ533 as primary immunosuppressant in a calcineurin(CNI)-free regimen in de novo kidney transplant (KTx) recipients.
Method: CFZ533 is a fully human, Fc-silenced, non-depleting, IgG1 mAb preventing CD40 pathway signaling and activation of CD40+ cell types. NCT02217410 is a 12-month multicenter randomized controlled Phase 2a clinical trial evaluating efficacy, safety, tolerability, and pharmacokinetics of CFZ533 (CFZ) in combination with mycophenolate mofetil (MMF) and corticosteroids (CS) compared with tacrolimus (TAC), MMF and CS in de novo KTx recipients. All patients received aIL-2 induction with basiliximab and corticosteroids as per center practice; a central, blinded pathologist reviewed all allograft biopsies.
Results: N=51 patients (pts) were transplanted and randomized (2:1) to either CFZ (N=33) or TAC (N=18). Twenty-five of 51 pts (49%) received a living donor allograft. After CD40 target saturation, CFZ was dosed IV every 4 weeks. CFZ was well tolerated with no infusion related nor thromboembolic events, and prospective Month 6 interim results demonstrated comparable efficacy on the composite endpoint of treated biopsy proven acute rejection, graft loss, or death (21.2 vs. 22.2%) and better renal function (55.8 vs. 45.5 mL/min) [Fig 1], less serious adverse events (SAE) (47.1 vs. 61.1%) and fewer infectious complications (50.0 vs. 77.8%) with no increase of opportunistic infections (viral overall: 26.5 vs. 50.0%; SAE CMV: 2.9 vs. 11.1%; BKV: 15.2 vs. 22.2%), and a lower rate of new-onset diabetes mellitus (14.7 vs. 38.9%) with CFZ vs. TAC, respectively.
Conclusion: CFZ533, a new anti-CD40 monoclonal antibody may have potential to become an effective CNI-free treatment for kidney Tx recipients improving transplant outcomes by preventing graft rejection without nephrotoxic (and other) CNI adverse effects. 12-month final study data will become available in Q1/2018 and will be presented at the 2018 TTS.

Figure 1: Evolution of renal function measured as eGFR (mL/min)