Rubic-Schneider, Tina, Ledieu, David, Garcia, Deborah, Hehlen, Jeannine, Cochin de Billy, Benjamin, Greutmann, Barbara, Kroener, Frieder, Verneret, Melanie, Bruederle, Andreas, Dajee, Maya, Burnet-Merlin, Coline, Kaminski, Tomasz W, Tomasz, Brzoska, Hines, Patrick C, Gao, Xiufeng, Sundd, Prithu, Bergeron, Renee, DeLise, Anthony, Dubey, Rikesh K and Pradhan-Sundd, Tirthadipa (2025) Crizanlizumab and inclacumab are equally potent inhibitors of cell adhesion in the blood of patients with sickle cell disease. Blood Red Cells & Iron.

Abstract

Acute painful vaso-occlusive episodes (VOEs) are the primary reason for emergency
department visit by sickle cell disease (SCD) patients and contribute to significant morbidity
in SCD. Crizanlizumab, a first-in-class humanized anti-P-selectin IgG2 monoclonal antibody,
is approved in more than 40 countries for prevention of VOEs in 16 years or older SCD
patients. Inclacumab, a fully human anti-P-selectin IgG4 mAb in clinical development is
believed to have stronger affinity to P-selectin and greater maximal inhibition of cell–cell
interactions than crizanlizumab. Using in vitro blinded experiments, we investigated whether
crizanlizumab and inclacumab can be differentiated in terms of P-selectin binding affinity
and inhibition of P-selectin-mediated cell adhesion in blood samples from healthy volunteers
or SCD patients. Surface Plasmon Resonance revealed that inclacumab had higher P-selectin
binding affinity than crizanlizumab, however, the inhibition of P-selectin-mediated cell
adhesion was higher or comparable with crizanlizumab than inclacumab. Crizanlizumab and
inclacumab were comparable in inhibiting leukocyte and erythrocyte adhesion to P-selection
under vascular mimetic flow in microfluidic channels, leukocyte-platelet aggregation, and
platelet aggregation in SCD patient or control human blood. In summary, these results
suggest that comparable or higher inhibition of cell adhesion with crizanlizumab vs
inclacumab does not correlate with P-selectin binding affinity. Ultimately, clinical trials are
required to evaluate how crizanlizumab vs inclacumab translate into treatment outcomes in
SCD patients.

Item Type:	Article
Date Deposited:	06 Nov 2025 00:45
Last Modified:	06 Nov 2025 00:45
URI:	https://oak.novartis.com/id/eprint/55750