FDA reviewing Casgevy for children with sickle cell as young as 5
Gene-editing therapy currently approved in US for patients 12 and older
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The U.S. Food and Drug Administration is reviewing an application from Vertex Pharmaceuticals seeking approval of Casgevy (exagamglogene autotemcel) for children with sickle cell disease (SCD) as young as 5 years old.
The gene-editing therapy is currently approved in the U.S. and elsewhere for people ages 12 and older with SCD and recurrent vaso-occlusive crises (VOCs).
Vertex’s new application was submitted using a Commissioner’s National Priority Voucher, which shortens a standard 10-month review time down to one or two months. Similar applications have been submitted in the U.K. and Saudi Arabia.
The applications to expand Casgevy’s approved age range are backed by data from the Phase 3 CLIMB-151 trial (NCT05329649), which showed that all Casgevy-treated children in that age group are free from VOCs.
“The data … underscore the consistent, durable and transformative benefits Casgevy can provide to people living with sickle cell disease … from early in life,” Carmen Bozic, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex, said in a company press release.
The company is also seeking to expand Casgevy’s eligible age range for people with transfusion-dependent beta thalassemia (TDT), a related blood disorder for which the therapy is also approved.
Data from CLIMB-151 and a similar trial in TDT patients were recently presented at the European Hematology Association (EHA) Congress and simultaneously published in the New England Journal of Medicine in a study, titled “Exa-cel in Children with Transfusion-Dependent [beta-Thalassemia] or Sickle Cell Disease.”
The study was sponsored by Vertex and CRISPR Therapeutics, the therapy’s co-developers, and some authors were affiliated with Vertex.
Casgevy designed to increase levels of fetal hemoglobin
SCD is caused by genetic mutations that lead to the production of a faulty version of hemoglobin, the protein that helps red blood cells carry oxygen. Consequently, red blood cells assume an abnormal shape, are destroyed faster, and can clump in blood vessels, interrupting blood flow and causing pain episodes known as VOCs. TDT is a related condition in which the body does not make enough hemoglobin.
“Despite optimized supportive therapy, children living with sickle cell disease and transfusion‑dependent beta thalassemia carry a significant disease burden from a very young age, with progressive complications leading to the irreversible and life-shortening consequences of these diseases,” said Franco Locatelli, MD, PhD, the study’s senior author, presenter of the trial data at the EHA, and director of the department of pediatric hematology and oncology at Bambino Gesù Children’s Hospital in Italy.
Casgevy is a gene-editing therapy designed to increase levels of fetal hemoglobin. This version of the protein is produced during fetal development and is not affected by SCD-causing mutations, but its production stops six to 12 months after birth.
The therapy involves collecting blood stem cells from a patient, engineering them in the lab to produce fetal hemoglobin, and then returning them to the patient through a stem cell transplant.
All 11 children were free from vaso-occlusive crises
CLIMB-151 is testing Casgevy in children, ages 2-11, with severe SCD, who were recruited at sites in the U.S. and Europe. The published data concerned the 11 participants ages 5 to 11 who received the therapy. They had a mean age of 8.5 years and had experienced a mean of two VOCs per year in the two years before the study’s start.
Overall, data showed that Casgevy had safety and efficacy profiles consistent with those observed in adult and adolescent patients.
After treatment, all 11 children were free from VOCs. Of the eight children (73%) with sufficient follow-up data, none experienced VOCs for at least 12 consecutive months, meeting the study’s main goal. They’ve been VOC-free for a median of 19 months, or about 1.5 years.
Those eight children were also free from hospitalization for severe VOCs for at least a year after the one-time therapy.
Among the 11 participants, Casgevy led to increases in fetal hemoglobin that allowed patients to reach normal levels of total hemoglobin as early as three months after treatment.
Safety data showed that most adverse events were consistent with those associated with a stem cell transplant procedure and comparable to those observed in older SCD patients.
The study also included data from a similar Phase 3 trial, dubbed CLIMB-141 (NCT05356195), which found the therapy to be just as effective in children with TDT.
“These data represent a profoundly important step forward, and I look forward to the possibility of providing earlier intervention to prevent complications in children and for families who have had limited potentially curative options to date,” Locatelli said.
After completing either CLIMB-151 or CLIMB-141, children could choose to enter CLIMB-131 (NCT04208529), a 13-year follow-up study to track long-term outcomes after Casgevy treatment.
