FDA expands approval of sickle cell gene therapy to patients as young as 2
Casgevy has previously only been available to patients 12 and older in US
Written by |
Casgevy (exagamglogene autotemcel) is now approved in the U.S. to treat children as young as 2 with sickle cell disease (SCD) and recurrent vaso-occlusive crises (VOCs).
The U.S. Food and Drug Administration (FDA) initially approved the Vertex Pharmaceuticals’ gene-editing therapy in 2023 for SCD patients ages 12 and older who experienced recurrent painful episodes known as VOCs. With this decision, Casgevy becomes the first gene-editing therapy approved for children as young as 2 with the disease.
The FDA has also expanded the therapy’s approval to include children as young as 2 with transfusion-dependent beta thalassemia (TDT), a related blood disorder for which Casgevy was also already approved.
While Vertex had requested a label expansion to include children as young as 5, the FDA considered that the therapy’s characteristics and latest clinical trial data in SCD patients, ages 5 to 11 years, allowed an extrapolation to children as young as 2 years.
“Pediatric patients as young as 2 years of age can now access a critical additional treatment option to treat these debilitating, life-threatening diseases,” Karim Mikhail, acting director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in an agency press release.
CEBR regulates biological therapies, or those derived from living organisms, like Casgevy, for human use.
“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, a specialist in pediatric blood diseases and the acting deputy director of CBER’s Office of Therapeutic Products.
About 5,500 additional children now eligible for one-time treatment
Casgevy is currently available for eligible patients through more than 75 authorized treatment centers across the U.S., and the expanded approval makes about 5,500 additional children in the country eligible for the one-time treatment, according to Vertex. Regulatory reviews of similar label expansion requests are also underway in the U.K. and Saudi Arabia.
“Our ambition is to transform the future for people living with sickle cell disease and transfusion-dependent beta thalassemia,” Reshma Kewalramani, MD, Vertex’s CEO and president, said in a company press release. “The remarkable consistency of results across age groups reinforces the potential of CASGEVY to deliver durable, transformative benefits to those who have historically had limited options.”
SCD is caused by genetic mutations that lead to the production of an abnormal version of hemoglobin, the protein that helps red blood cells carry oxygen. As a consequence, red blood cells become rigid and sickle-shaped, making them more likely to break apart and block blood vessels, triggering VOCs.
TDT occurs when the body cannot produce enough hemoglobin. Over time, both conditions can cause progressive organ damage and other serious complications that affect long-term health and life expectancy.
Casgevy designed to increase levels of fetal hemoglobin
Casgevy is designed to increase levels of fetal hemoglobin, the form of hemoglobin produced before birth that is not affected by SCD-causing mutations. Its production normally stops within the first six to 12 months of life.
The one-time therapy involves collecting a patient’s blood-forming stem cells, editing them in the laboratory to restore fetal hemoglobin production, and then returning the edited cells to the patient through a stem cell transplant.
The expanded approval for SCD was supported by results from the ongoing Phase 3 CLIMB-151 clinical trial (NCT05329649), which was designed to test Casgevy in children, ages 2 to 11 years, with severe SCD (two of more VOCs per year in the two years prior).
The youngest age at enrollment of the 11 participants was 5 years (mean age, 8.5 years). After a median of 16.9 months (nearly 1.5 years), all 11 treated children remained free of VOCs.
“Earlier access to the transformative potential of this therapy will allow clinicians and families to consider treatment before years of cumulative damage from these life-shortening diseases take hold.
None of the eight children with sufficient follow-up data experienced VOCs for at least 12 consecutive months, meeting the trial’s primary objective. They remained VOC-free for a median of 19 months (about 1.5 years), and none required hospitalization for severe VOCs during that period.
The therapy’s safety profile was consistent with that previously observed in older SCD patients, with most reported adverse events related to the stem cell transplant procedure.
While there were no data available for patients as young as 2 years, the FDA concluded that the therapeutic benefits seen in those as young as 5 could be extrapolated to younger children.
Casgevy’s label expansion “offers renewed hope for children living with sickle cell disease or transfusion‑dependent beta thalassemia,” said Haydar Frangoul, MD, medical director of HCA Healthcare’s Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Children’s Hospital and a member of Vertex’s SCD program steering committee. “Earlier access to the transformative potential of this therapy will allow clinicians and families to consider treatment before years of cumulative damage from these life-shortening diseases take hold.”
Leave a comment
Fill in the required fields to post. Your email address will not be published.