In a groundbreaking move, the United States Food and Drug Administration (FDA) has granted approval for a gene-editing treatment targeting sickle cell patients aged 12 years and above. The two-stage treatment, named Casgevy and Lyfgenia, represents a pioneering advancement in cell-based gene therapies for individuals grappling with sickle cell disease.
Casgevy, notably, stands out as the inaugural FDA-approved treatment employing CRISPR/Cas9, a cutting-edge genome editing technology. Nicole Verdun, the director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, expressed enthusiasm about the approval, stating, “Sickle cell disease is a rare, debilitating and life-threatening blood disorder with significant unmet need, and we are excited to advance the field, especially for individuals whose lives have been severely disrupted by the disease by approving two cell-based gene therapies today.”
Verdun emphasized the potential of gene therapy in providing more targeted and effective treatments, particularly for those with rare diseases facing limited current treatment options.
Casgevy, a cell-based gene therapy, is tailored for sickle cell disease treatment in patients aged 12 and older experiencing recurrent vaso-occlusive crises. The therapy utilizes CRISPR/Cas9 technology to modify patients’ hematopoietic stem cells, offering a precise and innovative approach to editing DNA.
The modified blood stem cells are reintroduced into the patient, engrafting within the bone marrow and increasing the production of fetal hemoglobin (HbF). Elevated levels of HbF, a type of hemoglobin facilitating oxygen delivery, help prevent the sickling of red blood cells in patients with sickle cell disease.
Another component of this groundbreaking approval is Lyfgenia, a cell-based gene therapy using a lentiviral vector for genetic modification. Lyfgenia is sanctioned for treating patients aged 12 and older with sickle cell disease and a history of vaso-occlusive events. The therapy modifies the patient’s blood stem cells to produce HbAT87Q, a gene-therapy-derived hemoglobin with functions akin to hemoglobin A found in individuals unaffected by sickle cell disease.
Both Casgevy and Lyfgenia involve a one-time, single-dose infusion as part of a hematopoietic stem cell transplant, utilizing the patient’s own blood stem cells that undergo modification. Prior to treatment, patients undergo myeloablative conditioning involving high-dose chemotherapy to replace cells from the bone marrow with the modified cells.
Given the significance of this development, patients receiving Casgevy or Lyfgenia will be closely monitored in a long-term study to assess the safety and effectiveness of each product. Sickle cell disease, affecting around 100,000 individuals in the United States, particularly among African Americans, has now seen a ray of hope with this unprecedented approval of innovative gene therapies.