ORLANDO, Fla. — Exagamglogene autotemcel (exa-cel, Casgevy), a CRISPR/Cas9 gene-editing therapy, showed efficacy in children aged 5-11 years with transfusion-dependent beta-thalassemia (TDT) or sickle cell disease (SCD), according to a pair of ongoing phase 3 trials.

Haydar Frangoul, MD, MS, Sarah Cannon Center Research Institute at The Children’s Hospital at TriStar Centennial, Nashville, Tennessee, presented e arly results from both the CLIMB SCD-151 trial and the CLIMB THAL-141 trial at the American Society of Hematology (ASH) 2025 Annual Meeting.

“Exa-cel has the potential to provide a one-time functional cure for children 5-11 years with TDT or [SCD] and has potential for greater benefit by treating them before they develop chronic organ damage,” said Frangoul, one of the authors of both studies, during a media briefing at the meeting.

A one-time, autologous cell therapy that reactivates fetal hemoglobin synthesis through ex vivo CRISPR/Cas9 editing of hematopoietic stem and progenitor cells, exa-cel is currently approved for individuals aged 12 years or older with TDT or with SCD and recurrent vaso-occlusive crises (VOCs), noted Frangoul.

The CLIMB THAL-141 Trial

The CLIMB THAL-141 trial enrolled 13 children aged 5-11 years with TDT with a history of ≥ 100 mL/kg/y or ≥ 10 U/y of packed red blood cell transfusions for 2 years before screening (mean age, 7.4 years; 61.5% boys).

Exa-cel was infused following pharmacokinetically (PK)-adjusted busulfan myeloablation in all 13 patients. The primary endpoint is transfusion independence for 12 or more consecutive months while maintaining a weighted average hemoglobin 9 g/dL or more.

As of data cutoff in July 2025, 12 of 13 patients had stopped transfusions at a mean 1.3 months after exa-cel infusion.

The six children with TDT who were evaluable for the primary endpoint didn’t need transfusions for at least 12 consecutive months (mean duration, 19.8 months).

However, two of 13 patients (15.4%) in the trial developed veno-occlusive disease of the liver.

“Unfortunately, one pediatric participant with TDT died of pneumonia in the setting of multi-organ failure, secondary to veno-occlusive disease of the liver,” Frangoul said. The death was attributed to busulfan conditioning.

The CLIMB SCD-51 Trial

The CLIMB SCD-151 trial enrolled 11 patients with SCD with a history of two or more severe VOCs per year for 2 years before screening (mean age, 8.5 years; 45.5% boys).

As in the CLIMB-THAL-141 study, exa-cel was infused in study participants following PK-adjusted busulfan myeloablation. The primary endpoint of the trial is the proportion of patients free of VOCs for 12 or more consecutive months.

In the four participants who were evaluable for the primary endpoint, all four were free of VOCs for at least 12 months following exa-cel infusion. The patients also met the secondary endpoint of being free from inpatient hospitalizations for at least 12 months.

In both of the trials, the safety profile was consistent with that of older patients who underwent gene therapy and with the safety profile of myeloablative busulfan conditioning and hematopoietic stem cell transplantation, the researchers reported in their abstract.

‘So Far, So Good’

Jaap Jan Boelens, MD, PhD, chief of Transplantation and Cellular Therapies and professor of pediatrics at Weill Cornell Medical College of Cornell University, New York City, who was not involved with the study, told Medscape Medical News that the results are “promising” with “solid data.”

The findings are similar to those in patients aged 12 years or older, he added.

In the big picture, matched sibling donor transplants remain the standard of care, Boelens said. But gene therapy is “potentially a good, transformative treatment solution for young TDT and SCD patients, in particular, if no matched sibling donor is available. What it will look like in the long run needs to be determined. But so far, so good.”

At another media briefing, hematologist-oncologist Belinda Avalos, MD, president of ASH and professor of medicine at Atrium Health Levine Cancer Institute, Charlotte, North Carolina, was asked how clinicians should choose between gene therapy and stem cell transplant in TDT and SCD.

“I don’t think we yet have a really good answer,” she said. “We have these as options, and it should be a shared decision-making process between the physician and the patient — or parents in the case of children. But certainly, factors that should be taken into consideration are whether the patient has experienced acute chest syndrome, recurrent vaso-occlusive crises, or stroke.”

She added that “we do know that transplantation has a long history of being effective. There have been concerns about graft-vs-host disease, which is why it’s not been implemented as much, and also donor availability, which has become much better.”

She added that “gene therapy looks very exciting,” but she noted that it has only been available for a short time.

Vertex funded the trials. Frangoul disclosed having relationships with Jazz, Vertex, Editas Medicine, BioLine, and Rocket Pharma. Some other authors reported having various disclosures. Boelens disclosed having relationships with Sobi, Sanofi, Rocket Pharma, Alexion, Papillion, Merck and DMC, CTI, and Advanced Clinical. Avalos disclosed having relationships with Juno and BMJ Best Practice.