Regulators approve first CRISPR-based therapy — exagamglogene autotemcel cleared
- The first CRISPR-based medicine was cleared in 2023, not today: the U.K. authorized Casgevy on November 16, 2023, and the U.S. Food and Drug Administration approved it on December 8, 2023. - Casgevy, or exagamglogene autotemcel, is made by Vertex Pharmaceuticals and CRISPR Therapeutics for patients 12 and older with sickle cell disease, and later won a second U.S. approval for transfusion-dependent beta thalassemia. - The approval established a regulatory route for genome editing after years of clinical testing in rare blood disorders. (fda.gov)
Casgevy became the first approved treatment that uses CRISPR gene editing when the U.K. cleared it on November 16, 2023, followed by a U.S. Food and Drug Administration approval on December 8, 2023. (crisprtx.com) (fda.gov) CRISPR works like molecular scissors: doctors collect a patient’s own blood stem cells, edit DNA outside the body, and return those cells after chemotherapy clears space in the bone marrow. Casgevy targets a DNA switch called BCL11A so the body makes more fetal hemoglobin, a form of oxygen-carrying protein that can reduce sickling. (fda.gov 1) (fda.gov 2) The first U.S. approval covered sickle cell disease in patients 12 and older with recurrent vaso-occlusive crises, the painful blockages that send many patients to the hospital. On January 16, 2024, the Food and Drug Administration expanded Casgevy to transfusion-dependent beta thalassemia, another inherited blood disorder. (fda.gov) (drugs.com) In the pivotal sickle cell study cited by regulators, 29 of 31 evaluable patients were free of severe vaso-occlusive crises for at least 12 consecutive months during follow-up. In transfusion-dependent beta thalassemia, 32 of 35 evaluable patients avoided red-blood-cell transfusions for at least 12 consecutive months. (fda.gov) (casgevyhcp.com) The treatment is not a simple infusion. Patients must first have stem cells collected, then receive myeloablative conditioning chemotherapy with busulfan, then wait for the edited cells to engraft, a process that can bring risks including infection, low blood counts, and mouth sores. (fda.gov) European regulators followed the U.K. and U.S. approvals in early 2024. The European Commission approved Casgevy on February 13, 2024, after the European Medicines Agency backed its use for severe sickle cell disease and transfusion-dependent beta thalassemia in eligible patients 12 and older. (crisprtx.com) (ema.europa.eu) The approval did not end the debate over access. Vertex said about 16,000 U.S. patients 12 and older with severe sickle cell disease could be eligible, but treatment requires specialized centers and lengthy hospital-based care. (investors.vrtx.com) (fda.gov) Casgevy’s clearance settled a question that had hung over CRISPR medicine for more than a decade: whether regulators would license a product built on direct genome editing. They did, first in Britain and then in the United States, with rare blood diseases opening the door. (crisprtx.com) (fda.gov)
