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4997 Improvements in Health-Related Quality of Life after Exagamglogene Autotemcel in Patients with Transfusion-Dependent Beta-ThalassemiaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 801. Gene Therapies: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Thalassemia, Hemoglobinopathies, Diseases, Gene Therapy, Therapies, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Franco Locatelli, MD, PhD1, Peter Lang, MD, PhD2*, Selim Corbacioglu, MD, PhD3*, Donna Wall, MD4, Amanda M Li, MD5, Josu de La Fuente, PhD6, Puja Kohli, MD, MMSc7*, Nanxin Li, PhD, MBA7, Jaime Rubin, MA, MPH7*, Siyu Zhang, PhD7*, Lanju Zhang, PhD7*, William Hobbs, MD, PhD7 and Haydar Frangoul, MD8

1IRCCS, Ospedale Pediatrico Bambino Gesù Rome, Catholic University of the Sacred Heart, Rome, Italy
2University of Tübingen, Tübingen, Germany
3University of Regensburg, Regensburg, Germany
4SickKids, Toronto, Canada
5BC Children’s Hospital, University of British Columbia, Vancouver, Canada
6Imperial College Healthcare NHS Trust, St Mary's Hospital, London, United Kingdom
7Vertex Pharmaceuticals, Boston, MA
8Sarah Cannon Research Institute at The Children’s Hospital at TriStar Centennial, Nashville, TN

Background: Transfusion-dependent β-thalassemia (TDT), an inherited hematological disorder which requires life-long, chronic red blood cell transfusion (RBC) and regular iron chelation therapy, has a substantial negative impact on health-related qualify of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, non-viral, ex vivo CRISPR-Cas9 gene-edited cell therapy in phase 3 clinical trials that has been shown to eliminate the need for RBC transfusions and achieve transfusion independence. Here, we report HRQoL data from a pre-specified interim analysis of the exa-cel CLIMB TDT-111 study.

Methods: CLIMB TDT-111 is an ongoing, 24-mo, phase 3 trial of a single dose of exa-cel in patients aged 12-35 years with TDT and a history of ≥100 mL/kg/year or ≥10 U/year of packed RBC transfusions for 2 years prior to screening. Changes in patient-reported outcome (PRO) measures including EuroQol Quality of Life Scale 5 dimensions 5 levels of severity (EQ-5D-5L, including descriptive system and visual analog scale [VAS]) and Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]) for adults and the EuroQol Quality of Life Scale 5 dimensions youth (EQ-5D-Y) and Pediatric Quality of Life Inventory (PedsQL) for adolescents were assessed through month 24 as a secondary endpoint in the trial. Data are presented as of 16 January 2023 for the 24 adults (aged ≥18-35 years) and 11 adolescents (aged ≥12 to < 18 years) who had been followed for ≥16 months after exa-cel infusion.

Results: Clinically meaningful improvements, exceeding the minimal clinically important difference (MCID) thresholds, were observed in all PRO measures in adults. Baseline mean EQ-5D-5L health utility US index score (n=24, mean [SD]: 0.85 [0.18]) was near the general population norm and in line with baseline scores previously reported for adult patients with TDT. By month 24, both EQ-5D-5L health utility US index scores and EQ VAS scores showed substantial improvement (mean [SD] changes at month 24 [n=15]: 0.12 [0.26] and 10.2 [20.9] points; MCIDs 0.078 and 7 to 10, respectively). FACT-G Total Score improved from baseline by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 10.3 [17.0] points; MCID 3 to 7), with improvements observed in all 4 subscales (physical, social/family, emotional, and functional well-being). BMTS score improved by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 6.8 [4.7] points; MCID 2 to 3).

For adolescents, EQ VAS scores improved through month 18 (mean [SD] change from baseline 4.8 [6.1] points). Total PedsQL score improved by month 6 and was sustained through month 18 (mean [SD] change from baseline [n=7] 14.1 [9.2] points; MCID 4.36). Physical functioning and psychosocial health scores, sub-components of PedsQL, both showed sustained improvement through month 18 (mean [SD] change [n=7] 19.2 [9.1] and 11.4 [10.9] points; MCID of 6.66 and 5.30 points, respectively). Improvement in psychosocial score was observed in all 3 subscales (social, emotional, and school functioning).

Conclusion: Adults and adolescents infused with exa-cel reported sustained and clinically meaningful improvements in their HRQoL, with improvements observed across different instruments and domains, including physical, emotional, social/family and functional well-being and overall health status. These results demonstrate the broad clinical benefits of exa-cel in patients with TDT.

Disclosures: Kohli: Vertex Pharmaceuticals: Current Employment. Li: Vertex Pharmaceuticals: Current Employment. Rubin: Vertex Pharmaceuticals: Current Employment. Zhang: Vertex Pharmaceuticals: Current Employment. Zhang: Vertex Pharmaceuticals: Current Employment. Hobbs: Vertex: Current Employment. Frangoul: Jazz Pharmaceuticals: Speakers Bureau; Editas Medicine: Consultancy; Rocket Pharmaceuticals: Consultancy, Other: Member of DSMB for a study; Vertex Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH