Exa-cel is showing great success in early pediatric studies on sickle cell anemia and beta-thalassemia

Exa-cel is showing great success in early pediatric studies on sickle cell anemia and beta-thalassemia

Preliminary results from two studies of the gene therapy Exagamglogene Autotemcel (Exa-Cel) suggest that the therapy offers an effective cure for beta thalassemia and sickle cell anemia in children under 12 years of age. Researchers say the therapy's potential to provide a cure at an early age - before organ damage accumulates - could make exa-cel even more beneficial in children than in adults.

All younger patients with adequate follow-up met the primary endpoint of being transfusion independent in patients with beta-thalassemia and free of vaso-occlusive crises in patients with sickle cell anemia. A 100 percent success rate is rare in anything we do.”

Haydar Frangoul, MD, medical director of pediatric hematology/oncology at the Sarah Cannon Research Institute at TriStar Centennial Children's Hospital in Nashville, Tennessee

Exa-cel is approved for patients 12 years and older who have transfusion-dependent beta-thalassemia or sickle cell anemia with recurrent vaso-occlusive crises (when blood cells get stuck in the vessels and cause severe pain and tissue damage). Both diseases are caused by genetic abnormalities that affect the blood's ability to carry oxygen throughout the body. exa-cel works by genetically modifying a patient's own blood stem cells to correct this abnormality.

For the treatment, blood stem cells are taken from patients, which are then genetically edited in the laboratory using CRISPR/Cas9. The patient then undergoes a chemotherapy-based conditioning regimen to cleanse the bone marrow before the genetically modified stem cells are implanted back into the body, where they begin creating healthy blood cells.

Researchers report preliminary results from two ongoing exa-cel studies in children ages 5 to 11. To date, the CLIMB THAL-141 trial has treated 13 patients with beta-thalassemia and the CLIMB SCD-151 trial has treated 11 patients with sickle cell disease.

In CLIMB THAL-141, six of 13 patients have so far been evaluated for the primary endpoint of transfusion independence for 12 consecutive months, meaning they maintained a weighted average hemoglobin level of 9 g/dL or higher without red blood cell infusion. All six reached this end point. In addition, participants showed an increase in hemoglobin and fetal hemoglobin production.

In CLIMB SCD-151, 4 of 11 patients have been evaluated to date for the primary endpoint of freedom from major vaso-occlusive crises and the secondary endpoint of freedom from inpatient treatment of major vaso-occlusive crises for 12 consecutive months. All four reached these endpoints. To date, no study participant has experienced a vascular occlusion crisis following exa-cel infusion. The increase in fetal hemoglobin production was similar to levels seen in teenagers and adults in previous studies, with average total hemoglobin levels reaching normal levels by the sixth month and remaining stable thereafter.

According to the researchers, the results not only show that gene therapy works in younger patients, but also suggest that it may be even more beneficial in this age group. "We think it might be better to treat them at an earlier age because it might prevent some irreversible complications that lead to chronic problems," said Dr. Frangoul.

Based on experience to date, the safety profile of therapy in these pediatric studies also appears to be consistent with studies in adolescents and adults, as well as the known side effects and complications associated with autologous stem cell transplantation and busulfan conditioning. A CLIMB THAL-141 study participant developed severe busulfan-related veno-occlusive disease with fatal multi-organ failure. Veno-occlusive disease is a known risk of busulfan and is more common in children. Despite decades of research on busulfan and alternative conditioning regimens associated with stem cell transplantation, there is no known strategy to completely eliminate this risk.

The CLIMB THAL-141 and CLIMB SCD-151 studies continue to recruit participants and track results to assess the safety and effectiveness of the therapy over a longer period of time and in a larger patient population. Dr. Frangoul noted that a future study could test the therapy in children ages two to four.

The CLIMB THAL-141 and the CLIMB SCD-151 Studies are sponsored by Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics.

Haydar Frangoul, MD, of the Sarah Cannon Research Institute at TriStar Centennial Children's Hospital, will present this study on Saturday, December 6, 2025, at 4:00 p.m. Eastern Time in W320 of the Orange County Convention Center.

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