FDA Expands Approval of First Gene Therapy for Young Children With Sickle Cell Disease

The U.S. Food and Drug Administration has granted supplemental approval to Casgevy for patients aged 2 years and older with sickle cell disease experiencing recurrent vaso-occlusive crises or with transfusion-dependent β-thalassemia. This marks the first gene therapy approved for children as young as 2 years with sickle cell disease, expanding access to a potentially curative treatment option for these inherited blood disorders.

Casgevy has been previously approved for the treatment of patients aged 12 years and older with SCD with recurrent VOCs or TDT.

“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 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 FDA Commissioner’s National Priority Voucher (CNPV) 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 affects red blood cells (RBCs), which contain hemoglobin, a protein that transports oxygen throughout the body. SCD can cause various symptoms and health issues, including episodes of severe pain called sickle cell crises or VOCs.

Thalassemia is a genetic blood disorder that causes the body to have an abnormally low level of hemoglobin, resulting in reduced oxygen delivery to the body’s tissues. In some cases, individuals require regular blood transfusions to maintain adequate levels of functional hemoglobin.

Casgevy is a gene therapy consisting of the patient’s own (autologous) hematopoietic (blood) stem cells, administered as a one-time single dose for intravenous infusion. The cells are edited using CRISPR/Cas9, a type of genome editing technology, and then engrafted in the body’s bone marrow. CRISPR/Cas9 can be directed to a specific spot in DNA, where it cuts the genetic material so that DNA can be accurately removed, added, or replaced. In patients with severe SCD, this treatment increases a type of hemoglobin which is called fetal hemoglobin (HbF). This helps prevent RBCs from forming into abnormal sickle shapes and addresses the underlying cause of disease, thereby eliminating VOCs.

In patients with TDT, treatment increases HbF levels and total hemoglobin levels, hence eliminating dependence on regular RBC transfusions.

Full myeloablative conditioning, a high-intensity preparatory treatment given to patients before they receive a stem cell transplant or gene therapy, is administered prior to treatment with Casgevy.

“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 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 safety and effectiveness of Casgevy in patients aged 5 years to less than 12 years with SCD were evaluated in a clinical trial which included 11 patients. All eight patients who were evaluable for efficacy achieved the primary efficacy outcome of VF12 (no protocol-defined severe VOCs for at least 12 consecutive months within the first 24 months after infusion with Casgevy).

The efficacy and safety of Casgevy in patients 5 years to less than 12 years of age with TDT were evaluated in a trial of 15 patients. Eight of the nine efficacy evaluable patients with TDT achieved transfusion independence for 12 consecutive months, with a median duration of transfusion independence of 20.1 months.

Based on product characteristics and clinical study data, extrapolation to the younger pediatric age population was granted to expand the indication to 2 years of age and above for both conditions.

The most common adverse reactions were mucositis (inflammation of mucous membranes) and febrile neutropenia (fever associated with low levels of a type of white blood cell called neutrophils) in patients with SCD and in patients with TDT, and decreased appetite in patients with SCD. Additionally, the prescribing information contains warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and off-target genome editing risk (refers to the possibility that the CRISPR/Cas9 editing process may make unintended edits to parts of the genome other than the intended target site).

The approval decision was granted just 53 days after filing and represented the eighth approval selected for the Commissioner's National Priority Voucher (CNPV) pilot program. The FDA granted Casgevy Orphan Drug, regenerative medicine advanced therapy (RMAT), and Fast Track designations.

The FDA granted the approval to Vertex Pharmaceuticals, Incorporated.