Exa-cel Exhibits Meaningful HRQoL Benefit in Severe Sickle Cell Disease

In 12 adolescents with at least 16 months of follow-up, receipt of exa-cel was associated with an improvement in general well-being in the EQ VAS and EQ-5D-5L US index scores at month 6, with respective mean differences of 4.1 points and 0.10 points.

Treatment with exagamglogene autotemcel (exa-cel; Gasgevy) exhibited a meaningful benefit to health-related quality of life (HRQoL) in 30 adult patients and 12 adolescent patients with severe sickle cell disease, according to results from the phase 3 CLIMB SCD-121 trial (NCT03745287) and the 13-year follow-up extension CLIMB-131 trial (NCT04208529) published in Blood Advances.¹

Of the 30 adult patients with at least 16 months of follow-up, substantial improvements exceeding minimal clinically important differences (MCIDs) for patient-reported outcome (PRO) measures were observed in the mean EQ VAS score after 6 months, with a mean change from baseline score of 17.7 points (SD, 26.5; MCID, 7-10; n = 27). After 6 months, the EQ-5D-5L health utility US index score improved for this population, with a mean change from baseline of 0.1 points (SD, 0.2; MCID, 0.078; n = 27). These improvements in both measures were generally maintained through month 36.

In 12 adolescents with at least 16 months of follow-up, receipt of exa-cel was associated with an improvement in general well-being in the EQ VAS and EQ-5D-5L US index scores at month 6, with respective mean differences of 4.1 points (SD, 34.9) and 0.10 points (SD, 0.90; n = 11). Furthermore, these improvements were sustained through month 24, with mean changes of 10.7 points (SD, 24.4) and 0.14 (SD, 0.26) points, respectively (n = 7).

In both adult and pediatric patients, the mean pain numerical rating scale score was improved by month 6, with a mean change from baseline of –0.9 points (SD, 3.3; MCID, –1; n = 27) and –1.1 points (SD, 2.1; n = 11) in the respective groups. In adults, this improvement was sustained through month 36, with a mean change of –1.8 points (SD, 2.1; n = 16); and in adolescents through month 24, with a mean change of –0.9 points (SD, 0.6; n = 8).

“Adults and adolescents with sickle cell disease had early, sustained, and clinically meaningful improvements in HRQoL measures following exa-cel infusion, with improvements seen across different instruments and domains, including physical, emotional, social/family, and functional well-being, pain experience, and overall health status,” study author Akshay Sharma, MBBS, MSc, physician in the Department of Bone Marrow Transplantation and Cellular Therapy at St. Jude’s Children’s Research Hospital wrote in the publication with study coinvestigators.¹ “These results confirm the broad clinical benefits of exa-cel, including associated improvements in quality of life and reductions in pain experience, in patients with severe sickle cell disease.”

The ongoing phase 3 CLIMB SCD-121 study enrolled patients aged 12 to 35 years with sickle cell disease with a history of 2 or more severe vaso-occlusive crises (VOCs) per year in the previous 2 years. Patients initially received plerixafor for hematopoietic stem and progenitor cell (HSPC) mobilization and apheresis for CD34-positive cell collection for gene editing. Exa-cel treatment was given via the intravenous route between 48 hours and 7 days.

Patients who completed the 2-year study period were permitted to enroll in the 13-year extension CLIMB-131 study.

The mean historical number of VOCs per year in a 2-year period prior to screening was 4.2 (SD, 3.1). The mean number of inpatient hospitalizations for VOCs was 2.8 (SD, 2.1).

The primary end point of the trial was the proportion of patients free from severe VOCs for 12 or more consecutive months. The key secondary end point was freedom from inpatient hospitalization for severe VOCs for at least 12 consecutive months. Additional secondary end points included change in baseline hemoglobin and fetal hemoglobin, duration of time free from VOCs, and changes in patient-reported outcome measures in adults and adolescents from baseline.

Reference

Sharma A, Locatelli F, Bhatia M, et al. Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel. Blood Adv. Published online August 26, 2025. doi:10.1182/bloodadvances.2025016701