The U.S. Food and Drug Administration has issued a supplemental approval for Casgevy (exagamglogene autotemcel), the first CRISPR/Cas9 gene therapy, for patients aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). Casgevy was previously approved for patients aged 12 and older.
“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., M.S., Acting Director of the FDA’s Center for Biologics Evaluation and Research (CBER). “The FDA is committed to prioritizing and speeding up the review of products that address critical U.S. health priorities through expedited review programs, including the Commissioner’s National Priority Voucher Pilot Program. These initiatives are designed to advance therapies for diseases with significant unmet medical needs, enabling faster access to innovative treatments while upholding the FDA’s rigorous gold-standard requirements for safety and effectiveness.”
SCD is a genetic blood disorder in which red blood cells assume an abnormal sickle shape, causing episodes of severe pain known as vaso-occlusive crises. Thalassemia causes the body to produce abnormally low levels of hemoglobin, requiring regular blood transfusions to maintain adequate oxygen delivery. Casgevy is manufactured from the patient’s own hematopoietic stem cells, which are edited using CRISPR/Cas9 technology to increase production of fetal hemoglobin (HbF). Higher HbF levels prevent red blood cells from sickling and reduce the need for transfusions.
The safety and effectiveness of Casgevy in patients 5 to less than 12 years of age were evaluated in separate clinical trials for each condition. In the SCD trial, all eight evaluable patients achieved the primary endpoint of freedom from severe VOCs for at least 12 consecutive months. In the TDT trial, eight of nine evaluable patients achieved transfusion independence for 12 consecutive months, with a median duration of 20.1 months. Based on product characteristics and clinical data, the FDA granted extrapolation to patients 2 years and older for both conditions.
The most common adverse reactions were mucositis, febrile neutropenia, and decreased appetite. The prescribing information includes warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and the risk of off-target genome editing, where CRISPR/Cas9 may make unintended edits elsewhere in the genome.
“These disorders carry a heavy burden for children and their families, affecting growth, development, and long-term health in profound ways,” said Megha Kaushal, M.D., MSc, Acting Deputy Director of the Office of Therapeutic Products in CBER and a pediatric hematologist. “Grounded in the scientific evidence that earlier treatment reduces the risk of lasting end-organ damage, making this therapy available to younger patients opens a critical window for intervention and gives these children a meaningful chance at a healthier future.”
The approval was granted just 53 days after filing and was the eighth selected for the FDA Commissioner’s National Priority Voucher (CNPV) pilot program, which aims to accelerate therapies for diseases with significant unmet medical needs. Casgevy previously received Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT), and Fast Track designations. Vertex Pharmaceuticals holds the approved application.
Source: FDA Press Release
