Casgevy safely prevents sickle cell crises in children: Trial data
Developers to seek expansion of gene-editing therapy's current indication
The gene-editing therapy Casgevy (exagamglogene autotemcel) safely and effectively prevents vaso-occlusive crises (VOCs) in children as young as 5 years old with severe sickle cell disease (SCD), according to preliminary data from a Phase 3 clinical trial.
As of the latest follow-up, all children in the CLIMB-151 (NCT05329649) trial, who range in age from 5 to 11 years, remained free of VOCs for up to two years after receiving the one-time therapy. The therapy’s safety profile has been consistent with that observed in prior studies in adults and adolescents.
The findings were shared in a presentation during the American Society of Hematology (ASH) Annual Meeting, being held Dec. 6-9 in Orlando, Florida, and virtually. The presentation was titled “First results of exagamglogene autotemcel in pediatric patients aged 5-11 years with transfusion-dependent [beta-thalassemia] or sickle cell disease with recurrent severe vaso-occlusive crises.”
“These results — the first clinical data ever presented on any genetic therapy for children ages 5-11 years with SCD — again demonstrate the transformative potential of Casgevy,” Carmen Bozic, MD, chief medical officer and executive vice president of global medicines development and medical affairs at Vertex Pharmaceuticals, which developed Casgevy in partnership with CRISPR Therapeutics, said in a company press release.
Casgecy recently received priority voucher from FDA
Based on these data, Vertex plans to submit applications seeking expansion of Casgevy’s current indication — covering SCD patients ages 12 and older who are experiencing recurrent VOCs — to those as young as 5 years.
“With dosing completed in the 5-11 age group and the Commissioner’s National Priority Voucher for CASGEVY in this population in hand, we are excited to begin global regulatory filings in the first half of next year and bring this potentially transformative therapy to eligible children as soon as possible,” Bozic said.
The priority voucher, recently received from the U.S. Food and Drug Administration, will shorten the regulatory review time from 10 months to one to two months.
SCD is a genetic disorder marked by an abnormal form of hemoglobin, the protein that red blood cells use to carry oxygen through the bloodstream. This abnormal hemoglobin is prone to forming clumps in red blood cells, which deforms them and makes them prone to getting stuck in blood vessels. This can disrupt normal blood flow, leading to painful VOCs.
Casgevy is a gene-editing therapy designed to increase levels of fetal hemoglobin, an alternative form of the protein produced during fetal development, but normally suppressed after birth.
The therapy works by collecting blood stem cells from a patient’s bone marrow, engineering them in a lab to boost fetal hemoglobin production, then returning them to the patient via a stem cell transplant.
Study participants free of VOCs since starting treatment
The international CLIMB-151 trial is testing Casgevy in up to 15 children ages 2 to 11 who have severe SCD and have experienced at least two severe VOCs per year in the two years prior.
All participants are receiving a single infusion of Casgevy and being followed for up to two years. The study’s main goal is to assess the proportion of children who are free from VOCs for at least one consecutive year.
The ASH presentation covered preliminary data from the 11 children in the 5- to 11-year-old age group. With follow-up times ranging from about three months to two years, none of these children have experienced a VOC since Casgevy treatment. All four children with sufficient follow-up met the main goal of being VOC-free for at least one year.
All younger patients with sufficient follow-up met the primary [goal] of being … free of vaso-occlusive crises. A 100% success rate is rare in anything that we do.
The treatment was also associated with a persistent increase in fetal hemoglobin levels.
Casgevy’s safety was consistent with the therapy’s known profile in older patients; most safety issues are in line with known side effects and risks associated with stem cell transplant procedures.
“All younger patients with sufficient follow-up met the primary [goal] of being … free of vaso-occlusive crises,” Haydar Frangoul, MD, the study’s lead author at TriStar Centennial Children’s Hospital in Nashville, Tennessee, said in an ASH press release. “A 100% success rate is rare in anything that we do.”
The trial may still be recruiting participants, ages 2 to 5 years, at sites in the U.S. and Europe. It is expected to end by mid-2026.
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