Improvements in Health-Related Quality of Life in Patients with Severe Sickle Cell Disease After Exagamglogene Autotemcel Open Access

• Infusion of exagamglogene autotemcel in patients with severe sickle cell disease improved overall health-related quality of life (HRQoL)

• Clinically-meaningful improvements in HRQoL and reductions in pain experience observed in both adults and adolescents across health domains

Severe sickle cell disease (SCD), an inherited blood disorder characterized by recurrent vaso-occlusive crises (VOCs), has substantial negative impact on health-related quality of life (HRQoL). Exagamglogene autotemcel (exa-cel), a one-time, ex vivo CRISPR/Cas9 gene-edited cell therapy, eliminated VOCs in 97% of participants with severe SCD in the Phase 3 CLIMB SCD-121 trial. Here, we describe changes in patient-reported outcomes (PRO) measures in 30 adults and 12 adolescents who had ≥16 months follow-up in CLIMB SCD-121. Adult PRO measures included EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L), Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and 11-point pain Numerical Rating Scale (NRS). In adolescents, EuroQol Quality of Life Scale-5 dimensions-youth (EQ-5D-Y), Pediatric Quality of Life Inventory (PedsQL), and pain NRS were used. Adult EQ-5D-5L health utility US and UK index and EQ VAS scores, which were lower than general population norm at baseline, substantially improved by Month 6 after exa-cel infusion and were sustained through Month 36, with similar improvements in FACT-G total and BMTS. All FACT-G (physical, social/family, emotional, functional well-being) and ASCQ-Me (emotional, social functioning, stiffness, sleep impact) subscales showed clinically meaningful improvement, including ASCQ-Me pain subscales (impact, episode frequency, severity), with substantial decreases in pain episode frequency by Month 6. Mean pain NRS score decreased by Month 6 and was sustained. Consistent with adults, adolescents had improvements in mean EQ-5D-Y VAS score, PedsQL score, and pain NRS. Exa-cel led to broad and clinically meaningful HRQoL benefits in adults and adolescents with SCD. (CLIMB SCD-121 and 131; Clinical Trials.gov numbers NCT03745287 and NCT04208529)