M.W.F. van den Hoogen, B. Nashan, H. Tedesco, S. Berger, D. Cibrik, S. Mulgaonkar, D. Leeser, R. Alloway, A. Patel, J. Pratschke, C. Sommerer, A. Wiseman, A.D. van Zuilen, U. Laessing, J. Rush, B. Haraldsson
Wednesday 13 march 2019
16:00 - 16:10h at Koningin Máximazaal
Categories: Best abstracts, Parallelsessie
Parallel session: Parallelsessie VI – Best abstracts I
Background: To assess the potential of CFZ533 (CFZ) as primary immunosuppressant in a calcineurin-inhibitor (CNI)-free regimen in de novo kidney transplant recipients
Methods: 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 CFZ in combination with mycophenolate mofetil (MMF) and corticosteroids (CS) compared with tacrolimus (TAC), MMF and CS in de novo kidney transplant recipients. All patients received induction with basiliximab and CS as per center practice.
Results: N=51 pts were transplanted and randomized (2:1) to either CFZ (N=33) or TAC (N=18). 25 of 51 pts (49%) received a living donor allograft. After CD40 target saturation, CFZ was dosed every 4 weeks. CFZ was well tolerated with no infusion related nor thromboembolic events. 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), 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. 12-month final study data will be available in the beginning of 2019.
Conclusions: CFZ533, a new anti-CD40 monoclonal antibody may have potential to become an effective CNI-free treatment for kidney transplant recipients improving transplant outcomes by preventing graft rejection without nephrotoxic (and other) CNI adverse effects.