Gene Therapy Improves Quality of Life for SCD, Beta Thalassemia

Substantial improvements seen across ages in overall health and wellbeing

(WASHINGTON — August 27, 2025) – Treatment with exagamglogene autotemcel (exa-cel) led to robust and sustained improvements in quality of life for patients with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia, according to two studies published in Blood Advances.

“This is the first time we’ve been able to measure improvements in quality of life after treatment with gene editing technology,” said Josu de la Fuente, PhD, director of the Paediatric Blood and Marrow Transplantation Programme at Imperial College London Healthcare NHS Trust, professor of practice (Cell & Gene Therapy) at Imperial College London, and lead author of the beta thalassemia study. “Most research on new therapies like exa-cel tends to focus on improvements in laboratory values, but what is most important to patients with severe SCD or transfusion-dependent beta thalassemia are improvements in their daily life.”

Participants in both studies reported clinically meaningful improvements in overall quality of life, including physical, social/family, functional, and emotional well-being. Sustained improvements were observed starting as early as six months following exa-cel infusion.

"This treatment has transformed lives and its impact was evident as we followed up with patients in our clinic,” said Haydar Frangoul, MD, MS, medical director of pediatric hematology/oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital and lead author of the SCD study. “Patients are returning to school, back to work, and overall spending more time with their families and less time in the hospital. It’s a powerful example of how clinical research drives real-world impact.”

The researchers used patient-reported outcome data from the CLIMB-SCD-121, CLIMB-THAL-111, and 13-year follow-up study, CLIMB-131, to evaluate quality-of-life improvements. Patients had at least 16 months of follow-up; median duration was 33.6 months in the SCD study and 38.4 months in the beta thalassemia study. The CLIMB-SCD-121 trial data included 42 adolescents and adults with severe SCD treated with exa-cel, and the CLIMB-THAL-111 trial data included 54 adolescents and adults with transfusion-dependent beta thalassemia.

In the SCD study, Dr. Frangoul and his colleagues evaluated outcomes using three quality of life assessments and one pain scale for adult patients, and two quality of life assessments along with one pain scale for adolescents. In both adult and adolescent patients, quality of life scores were below population norms prior to exa-cel infusion.

However, following treatment, scores across all domains exceeded population norms and surpassed thresholds for minimal clinically important difference (MCID) – the smallest change patients perceive as meaningful – indicating that patients experienced substantial, personally important improvements. Specifically, for adults, results from the ASCQ-Me quality of life scale, which is designed to measure SCD outcomes, showed the greatest non-pain improvements in social impact (+16.5), emotional impact (+8.5), and sleep impact (+5.7). For adolescents, PedsQL scores indicated improvements in school functioning (+45), social functioning (+18.3), and emotional functioning (+16.7) after infusion.

In the beta thalassemia study, Dr. de la Fuente and his colleagues used two quality of life scales to evaluate outcomes in adult patients and two quality of life scales for adolescent patients. Unlike for patients in the SCD study, average quality of life for adults and adolescents with beta thalassemia as measured by the EQ-5D-5L score, which provides a quantitative measure of overall health through five dimensions of health and ability, was near or higher than general population norms in adults prior to infusion (80.4 for U.S. populations).

At 48 months past infusion, adults had a mean score improvement of 14.0 from a baseline of 82.2 at infusion. For adolescents, baseline at infusion was 81.3, with a mean score improvement of 6.1 at month 24. For both adults and adolescents, treatment with exa-cel led to clinically meaningful improvements across all domains and surpassed MCID thresholds.

SCD and beta thalassemia are inherited blood disorders affecting hemoglobin, a protein in red blood cells responsible for carrying oxygen. SCD affects an estimated 100,000 Americans, while more than a million people worldwide are estimated to have beta thalassemia. Transfusion-dependent beta thalassemia requires consistent red blood cell transfusions to maintain adequate hemoglobin levels.

Exa-cel, a CRISPR-based gene therapy, removes a patient’s own blood-forming stem cells and edits them to produce healthy hemoglobin before being infused again into the patient. It is a one-time, curative therapy and received FDA approval in December 2023 for the treatment of severe SCD, and January 2024 for transfusion-dependent beta thalassemia, for patients ages 12 years and older.

“Although exa-cel is a complex and costly treatment, the significant improvements in quality of life shown in these studies make it a worthwhile investment, especially for younger patients, who showed marked improvements,” said Dr. de la Fuente. “These patients will now have the opportunity live normal, high-quality lives and contribute to their families, workplaces, and society.”

Given their reliance on patient-reported data, the studies have limitations, namely that some of their patient-reported outcome tools were not developed specifically for SCD or transfusion-dependent beta thalassemia. Additionally, these clinical trials remain ongoing, thus observed trends should be interpreted with caution.

The researchers plan to continue patient follow-up in larger study cohorts to validate their findings.

Blood Advances (bloodadvances.org) is an online, open-access journal publishing more peer-reviewed hematology research than any other academic journal worldwide. Blood Advances is part of the Blood journals portfolio (bloodjournals.org) from the American Society of Hematology (ASH) (hematology.org).

Claire Whetzel, 202-629-5085
cwhetzel@hematology.org