Vertex Pharmaceuticals and CRISPR Therapeutics have announced that the U.S. Food and Drug Administration (FDA) has approved CASGEVY (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 genome-edited cell therapy, for the treatment of sickle cell disease (SCD) in patients 12 years and older with recurrent vaso-occlusive crises (VOCs).
This approval means that for the first time, approximately 16,000 patients with SCD may be eligible for a durable one-time therapy that offers the potential of a functional cure for their disease by eliminating severe VOCs and hospitalisations caused by severe VOCs.
“CASGEVY’s approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the US. As importantly, CASGEVY is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “I want to convey my deepest gratitude to the patients and investigators whose trust in this programme paved the way for this landmark approval.”
The administration of CASGEVY requires specialised experience in stem cell transplantation; therefore, Vertex is engaging with experienced hospitals to establish a network of independently operated, authorised treatment centres throughout the US.
CASGEVY is a genome-edited cellular therapy consisting of autologous CD34+ hematopoietic stem cells (HSCs) edited by CRISPR/Cas9 technology at the erythroid-specific enhancer region of the BCL11A gene. CASGEVY is intended for one time administration via a haematopoietic stem cell transplant procedure where the patient’s own CD34+ cells are modified to reduce BCL11A expression in erythroid lineage cells, leading to increased foetal haemoglobin (HbF) production. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate vaso-occlusive crises for patients with SCD.
CASGEVY was granted a conditional marketing authorisation in Great Britain by the MHRA and by the National Health Regulatory Authority in Bahrain for patients 12 years of age and older with SCD characterised by recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia (TDT), for whom haematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available. CASGEVY is currently under review by the European Medicines Agency and the Saudi Food and Drug Agency for both SCD and TDT.
