The approval expands the use of Casgevy to patients as young as 2 years old for the treatment of sickle cell disease and beta thalassemia.
RT’s Three Key Takeaways:
- Expanded Age Indication: The FDA approved the first gene therapy for children as young as 2 years old with sickle cell disease or transfusion-dependent beta thalassemia.
- CRISPR Technology: The treatment uses CRISPR/Cas9 technology to edit a patient’s own blood stem cells to increase fetal hemoglobin levels, which prevents red blood cells from sickling and eliminates the need for transfusions.
- Clinical Efficacy: Clinical trials for pediatric patients showed that the majority of evaluable participants achieved the primary goals of eliminating severe pain crises or reaching transfusion independence, according to the news release.
The USFDA issued a supplemental approval for Casgevy (exagamglogene autotemcel) for patients aged 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises or transfusion-dependent beta thalassemia (TDT). According to the agency, this represents the first gene therapy approved for patients as young as 2 years old with SCD.
Casgevy was previously approved for the treatment of patients aged 12 years and older with SCD or TDT. The new decision allows younger pediatric patients to access an additional treatment option for these life-threatening diseases, said Karim Mikhail, B Pharm, MS, acting director of the Center for Biologics Evaluation and Research (CBER), in a news release.
Mikhail noted that the FDA is committed to speeding up the review of products that address critical US healthcare priorities through expedited review programs. These initiatives are designed to advance therapies for diseases with significant unmet medical needs, enabling faster access to treatments while upholding safety and effectiveness standards, according to the news release.
SCD affects red blood cells which contain hemoglobin, a protein that transports oxygen throughout the body. The condition can cause episodes of severe pain called sickle cell crises or vaso-occlusive crises. Thalassemia is a genetic blood disorder that causes low levels of hemoglobin, often requiring regular blood transfusions to maintain functional levels.
Casgevy is a gene therapy consisting of the patient’s own blood stem cells, which are administered as a one-time single dose for intravenous infusion. The cells are edited using CRISPR/Cas9 technology to increase fetal hemoglobin, which helps prevent red blood cells from forming abnormal sickle shapes and addresses the underlying cause of the disease, according to the FDA. In patients with TDT, the treatment increases total hemoglobin levels to eliminate dependence on regular red blood cell transfusions.
Safety and effectiveness in patients aged 5 to 12 years with SCD were evaluated in a clinical trial of 11 patients. All eight patients evaluable for efficacy achieved the primary outcome of no severe vaso-occlusive crises for at least 12 consecutive months. In a separate trial of 15 patients with TDT in the same age range, eight of the nine evaluable patients achieved transfusion independence for 12 consecutive months.
“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,” said Megha Kaushal, MD, MSc, acting deputy director of the Office of Therapeutic Products in CBER and pediatric hematologist, in a news release.
The most common adverse reactions included mucositis and febrile neutropenia in patients with SCD and TDT, and decreased appetite in patients with SCD. The prescribing information also contains warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions, and off-target genome editing risk, according to the FDA.
The approval was granted to Vertex Pharmaceuticals Inc 53 days after filing. The FDA granted the therapy Orphan Drug, regenerative medicine advanced therapy, and Fast Track designations.
