Gene Therapy Prevents Vaso-Occlusive Crises in Patients With SCD

A recent study in the New England Journal of Medicine demonstrated the efficacy of exagamglogene autotemcel (exa-cel), a CRISPR/Cas9 gene-edited cell therapy, in preventing vaso-occlusive crises in patients with sickle cell disease (SCD).

Investigators from the Children’s Hospital of Philadelphia led the trial, which included 44 patients and a median follow-up of 19.3 months. Of the 30 patients who had sufficient follow-up to be evaluated, 29 (97%) were free from vaso-occlusive crises for at least 12 consecutive months. All 30 were free from hospitalizations for vaso-occlusive crises for at least 12 consecutive months. The safety of exa-cel was comparable to treatment with hematopoietic and progenitor stem cells, and no malignancies were reported because of treatment.

Exa-cel, marketed as Casgevy by Vertex Pharmaceuticals, is the first FDA-approved therapy to utilize CRISPR-Cas9 genome editing technology. The therapy works by modifying patients’ hematopoietic stem cells to remove the gene responsible for SCD. Once reintroduced into the patient, these modified cells engraft within the bone marrow, leading to increased production of fetal hemoglobin (HbF). This in turn facilitates oxygen delivery and prevents red blood cell sickling.

Exa-Cel in Beta-Thalassemia

In a separate phase 3 study, investigators also reported promising outcomes in patients with beta-thalassemia. Among the 52 participants followed for a median period of 20.4 months, 32 (91%) achieved transfusion independence following exa-cel treatment.

During this period, patients experienced a mean total hemoglobin level of 13.1 grams per deciliter (g/dL) and a mean fetal hemoglobin level of 11.9 g/dL, with fetal hemoglobin demonstrating a widespread distribution among red cells (greater than 94%). The safety profile of exa-cel was consistent with that of myeloablative busulfan conditioning and autologous hematopoietic stem cell transplantation, with no reported fatalities or incidences of cancer.

In January, FDA approved exa-cel to treat beta-thalassemia based on preliminary results of the trial.