FDA Approves Innovative Cell-based Gene Therapy for Sickle Cell Disease

The US Food and Drug Administration (FDA) has approved exagamglogene autotemcel (exa-cel), a cell-based therapy approved for sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises, and the first FDA-approved therapy that utilizes CRISPR/Cas9 genome editing technology, according to the manufacturer, Vertex Pharmaceuticals.

Patients with SCD carry a hemoglobin mutation that causes the production of the eponymous sickle-shaped red blood cells. These cells impair blood flow and oxygen delivery, causing significant pain and organ damage.

Exa-cel, approved under the trade name Casgevy, is manufactured from a patient’s own hematopoietic stem cells. The use of CRISPR/Cas9 technology essentially allows mutated DNA to be cut, after which the modified hematopoietic stem cells are transplanted into the patient.

Once modified cells engraft in the bone marrow, they facilitate the production of fetal hemoglobin, the main type of hemoglobin that carries oxygen in human fetuses and infants. Data show increased fetal hemoglobin levels in patients with SCD prevents the production of sickled red blood cells.

“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,” said Nicole Verdun, MD, Director of the Office of Therapeutic Products in the FDA Center for Biologics Evaluation and Research.

Data backing the approval of exa-cel included an ongoing single-arm, multicenter trial that enrolled adult and adolescent patients with SCD and a history of at least two severe vaso-occlusive crises in each of the two years before screening.

Of the 31 patients eligible for evaluation after 24 months, 93.5% experienced no severe vaso-occlusive crises for at least 12 consecutive months. The most common side effects were low platelet and white blood cell counts, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia, headache, and itching.

“Gene therapy holds the promise of delivering more targeted and effective treatments, especially for individuals with rare diseases where the current treatment options are limited,” stated Dr. Verdun.