The U.S. Food and Drug Administration (FDA) has issued a supplemental approval expanding the use of Casgevy (exagamglogene autotemcel), a CRISPR/Cas9-based gene therapy, to include pediatric patients aged 2 years and older with sickle cell disease (SCD) characterized by recurrent vaso-occlusive crises (VOCs), or transfusion-dependent β thalassemia (TDT). The decision marks the first time a gene therapy has been approved for use in children as young as 2 with SCD, according to the agency.
Casgevy was previously authorized for patients aged 12 years and older. The expanded indication is based on clinical data in younger pediatric populations, along with extrapolation of product characteristics and study results.
Expanding access in early childhood
FDA officials emphasized the importance of earlier intervention for these genetic blood disorders. “With today’s decision, pediatric patients as young as 2 years of age can now access a critical additional treatment option to treat these debilitating, life-threatening diseases,” said Karim Mikhail, B Pharm, MS, acting director of the Center for Biologics Evaluation and Research (CBER).
He added that expedited review pathways, including the Commissioner’s National Priority Voucher (CNPV) Pilot Program, aim to accelerate access while maintaining regulatory standards for safety and effectiveness.
SCD is characterized by abnormal hemoglobin in red blood cells that can cause sickling, leading to VOCs and severe pain episodes. TDT results in insufficient hemoglobin production, often requiring lifelong blood transfusions.
How Casgevy works
Casgevy is an autologous hematopoietic stem cell gene therapy administered as a one-time intravenous infusion. Patient stem cells are edited ex vivo using CRISPR/Cas9 technology and then reinfused to engraft in the bone marrow. The edit increases production of fetal hemoglobin (HbF), which helps prevent sickling in SCD and improves hemoglobin levels in TDT.
In SCD, increased HbF reduces formation of sickled red blood cells and aims to eliminate VOCs. In TDT, higher hemoglobin production can reduce or eliminate transfusion dependence.
Patients must undergo full myeloablative conditioning prior to receiving therapy.
Clinical outcomes and safety
In pediatric trials, eight of eight evaluable SCD patients achieved the primary endpoint of no protocol-defined severe VOCs for at least 12 consecutive months within a 24-month period following infusion. In TDT studies, eight of nine evaluable patients achieved transfusion independence for at least 12 consecutive months, with a median duration of 20.1 months.
Common adverse reactions included mucositis, febrile neutropenia, and decreased appetite. Safety warnings include risks of neutrophil and platelet engraftment failure, hypersensitivity reactions, and potential off-target genome editing.
The FDA granted approval to Vertex Pharmaceuticals, Incorporated, under Orphan Drug, regenerative medicine advanced therapy (RMAT), and Fast Track designations, with review completed in 53 days under the CNPV pilot program.
Note: This news summary was generated by AI based on a published press release, followed by a review from human editors.
