Drug Interaction Report

GENERALLY AVOID: Crizanlizumab and voxelotor may affect the manufacturing and efficacy of the autologous genome edited hematopoietic stem cell (HSC)-based gene therapy, exagamglogene autotemcel. Patients must undergo CD34+ HSC mobilization followed by apheresis to isolate the CD34+ cells required for exagamglogene autotemcel production. After these cells are collected and exagamglogene autotemcel has been manufactured, patients will undergo myeloablative conditioning. Disease modifying therapies for sickle cell disease (e.g., hydroxyurea, crizanlizumab, voxelotor) were discontinued in clinical trials at the initiation of red blood cell exchange or simple transfusions, which took place at least 8 weeks prior to the start of mobilization and conditioning. Although not specifically mentioned in the product labeling, the disease modifying antioxidant therapy L-glutamine may also interfere with exagamglogene autotemcel. However, clinical data on the interaction potential of L-glutamine, crizanlizumab, and voxelotor with mobilization and conditioning agents are unavailable.

MANAGEMENT: The manufacturer recommends discontinuation of voxelotor and crizanlizumab at least 8 weeks prior to the start of both mobilization and conditioning because their interaction potential with mobilization and myeloablative conditioning agents is unknown. Until further information is available, it may also be advisable to discontinue treatment with L-glutamine after administration of exagamglogene autotemcel, as per clinical trial experience.