The CRISPR Solution for the Treatment of Sicke Cell Anaemia

A possible curative treatment for all patients with β-hemoglobinopathies, including sickle cell disease (SCD), is genome editing. Because naturally occurring hereditary persistence of hemoglobin (HbF) (HPFH) has been shown to alleviate disease symptoms and fetal hemoglobin (HbF) inhibits the polymerization of sickle hemoglobin (HbS), reawakening developmentally silenced HbF in adult red blood cells (RBCs) has long been considered a promising therapeutic approach.

Selami Demirci et. al. 2021 stated that advancements in genome editing have provided a tremendous understanding of transcriptional globin control, and targets of HbF regulation have shown clinical promise.

Similarly, on December 8, 2024, Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics stated 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 hospitalizations caused by severe VOCs. The 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 hematopoietic stem cell transplant procedure where the patient’s own CD34+ cells are modified to reduce BCL11A expression in erythroid lineage cells, leading to increased fetal hemoglobin (HbF) production. CASGEVY has been shown to reduce or eliminate vaso-occlusive crises for patients with SCD.

Furthermore, in conjunction with the FDA approval of CASGEVY, Vertex will make a $200 million milestone payment to CRISPR, which will be capitalized and amortized to the cost of sales.