The U.S. Food and Drug Administration has issued a supplemental approval for Casgevy (exagamglogene autotemcel), expanding its use to patients aged 2 years and older with sickle cell disease (SCD) with recurrent vaso-occlusive crises or transfusion-dependent β thalassemia (TDT). The decision marks the first gene therapy approved for patients aged 2 years and older with SCD.

According to a news release from the agency, the therapy had previously been approved for patients aged 12 years and older with either condition.

“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,” Acting Director of the Center for Biologics Evaluation and Research (CBER) Karim Mikhail, B. Pharm., M.S., said in the release. “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 is a genetic disorder affecting red blood cells, which carry hemoglobin, a protein responsible for transporting oxygen throughout the body. The condition can lead to anemia, organ damage and episodes of severe pain known as vaso-occlusive crises.

TDT is a genetic blood disorder that results in abnormally low hemoglobin levels, reducing oxygen delivery to tissues and in many cases requiring regular blood transfusions to maintain adequate hemoglobin.

Casgevy is a one-time gene therapy made from a patient’s own autologous hematopoietic stem cells, which are collected, edited using CRISPR/Cas9 genome editing technology and then infused back into the patient. The edited cells engraft in the bone marrow. CRISPR/Cas9 targets specific DNA sequences to cut genetic material so it can be removed, added or replaced. In patients with severe SCD, the therapy increases production of fetal hemoglobin (HbF), which helps prevent red blood cells from forming sickle shapes and reduces vaso-occlusive crises. In patients with TDT, increased HbF and total hemoglobin levels eliminate dependence on regular red blood cell transfusions.

Full myeloablative conditioning, an intensive preparatory regimen used before stem cell transplant or gene therapy, is required prior to Casgevy treatment.

“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 expanded approval was supported by clinical data in pediatric patients. In a study of 11 patients with SCD aged 5 years to less than 12 years, all eight evaluable patients achieved the primary efficacy outcome of VF12, defined as no protocol-defined severe vaso-occlusive crises for at least 12 consecutive months within the first 24 months after infusion with Casgevy.

In a separate trial of 15 patients with TDT aged 5 years to less than 12 years, eight of the nine efficacy evaluable patients achieved transfusion independence for 12 consecutive months, with a median duration of 20.1 months.

Based on these findings and product characteristics, the FDA allowed extrapolation of data to extend use to patients aged 2 years and older for both conditions.

The most common adverse reactions included mucositis and febrile neutropenia in both SCD and TDT patients, along with decreased appetite in SCD patients. The prescribing information also includes warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions and off-target genome editing risk, referring to the possibility that CRISPR/Cas9 may introduce unintended genetic changes outside the target site.

The FDA completed its review in 53 days after filing, making Casgevy the eighth approval selected under the Commissioner’s National Priority Voucher pilot program. The therapy also holds Orphan Drug, regenerative medicine advanced therapy and Fast Track designations.

The approval was granted to Vertex Pharmaceuticals, Incorporated.