Drug Interaction Report

ADJUST DOSING INTERVAL: Hydroxyurea may affect the manufacturing and therapeutic efficacy of the autologous hematopoietic stem cell-based gene therapy, lovotibeglogene autotemcel. The exact mechanism has not been described; but could be related to hydroxyurea's ability to interfere with DNA synthesis and/or its bone marrow suppressive effects, potentially reducing the number of hematopoietic stem cells (HSCs). Hematopoietic stem cell mobilization followed by apheresis is required to isolate the CD34+ cells needed for lovotibeglogene autotemcel production. Previous studies available in the medical literature have shown that hydroxyurea treatment is associated with a decreased level of CD34+ cells in both the peripheral blood and bone marrow. One study revealed that the number of peripheral blood CD34+ cells was 2.5 cells/microL of blood in hydroxyurea treated patients (n=31), 19 cells/microL in treatment naive patients (n=19) and those receiving chronic transfusions (n=19), and 7.3 cells/microL in the control group (individuals without sickle cell disease, n=25). Clinical data evaluating the use of hydroxyurea 2 months before the planned start of mobilization as well as after the receipt of lovotibeglogene autotemcel are not available.

MANAGEMENT: The manufacturer of lovotibeglogene autotemcel recommends discontinuation of hydroxyurea for at least 2 months prior to the start of each HSC mobilization cycle, and until all cycles of apheresis have been completed. If administered after apheresis, hydroxyurea should be discontinued at least 2 days prior to myeloablative conditioning. Additionally, there is no experience with the use of hydroxyurea after lovotibeglogene autotemcel infusion.