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4999 Improvements in Health-Related Quality of Life after Exagamglogene Autotemcel in Patients with Severe Sickle Cell DiseaseClinically Relevant Abstract

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

Akshay Sharma, MBBS1, Haydar Frangoul, MD2, Markus Mapara, MD3*, Suzan Imren, MD4*, Nanxin Li, PhD, MBA4, Tina Liu, PhD4*, Jaime Rubin, MA, MPH4*, Daoyuan Shi, PhD4*, William Hobbs, MD, PhD4 and Stephan Grupp, MD, PhD5

1St. Jude Children's Research Hospital, Memphis, TN
2Sarah Cannon Research Institute at The Children’s Hospital at TriStar Centennial, Nashville, TN
3Department of Medicine, Division of Hematology/Oncology, Columbia University, New York, NY
4Vertex Pharmaceuticals, Boston, MA
5Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA

Background: Severe sickle cell disease (SCD), which is characterized by recurrent vaso-occlusive crises (VOCs), has a substantial negative impact on health-related quality of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, non-viral, ex vivo CRISPR/Cas9 gene-edited autologous cell therapy in phase 3 clinical trials that has been shown to eliminate VOCs. Here, we report HRQoL data from a pre-specified interim analysis of the exa-cel CLIMB SCD-121 study.

Methods: CLIMB SCD-121 is an ongoing phase 3 trial of a single dose of exa-cel in patients ages 12-35 years with SCD and a history of ≥2 VOCs/year in each of the 2 years prior to screening. Changes in patient reported outcomes measures EuroQol Quality of Life Scale 5 dimensions 5 levels of severity (EQ-5D-5L, including descriptive system and visual analog scale [VAS]), Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and the 11-point pain Numerical Rating Scale (NRS ) were assessed from baseline through month 24 as a secondary endpoint in the trial. Data is presented as of 10 Feb 2023 for the 17 adult patients (aged ≥18-35 years) who had been followed for ≥16 months after exa-cel infusion.

Results: Substantial and clinically meaningful improvements exceeding minimal clinically important difference (MCID) thresholds were observed in all assessed patient reported outcomes measures. At baseline, the EQ-5D-5L health utility US index (n=17; mean [SD]: 0.71 [0.23]) and EQ VAS (63.5 [22.5]) scores were lower than the US general population norm and similar to baseline scores reported for adult SCD patients with recurrent VOCs. By month 6, both EQ-5D-5L health utility US index score and EQ VAS score showed substantial improvements, which were maintained through month 24 (mean changes [SD] at month 24 [n=8]: 0.23 [0.20]; MCID 0.078 and 28.3 [16.2]; MCID 7 to 10, respectively). FACT-G Total Score improved from baseline at month 24 (mean [SD] change at month 24 [n=8]: 29.8 [17.2]; MCID 3 to 7), with improvements observed in all 4 subscales (physical, social/family, emotional, and functional well-being). BMTS score improved by month 6 and was sustained through month 24 (mean [SD] change at month 24 [n=8]: 3.9 [5.7]; MCID 2 to 3). All subscales of the ASCQ-Me, including emotional (mean [SD] change [n=7] 17.7 [9.8]), social (23.8 [6.7]), stiffness (7.9 [12.9]), and sleep impact (8.4 [8.3]), demonstrated clinically meaningful improvements from baseline through month 24. For the ASCQ-Me pain-related subscales evaluating pain impact, pain episode frequency and pain severity, the largest numerical improvement was observed in pain episode frequency (mean [SD] change at month 24 [n=8]: -22.8 [8.2]; MCID -5). Improvements in the pain NRS were observed by month 12 and sustained through Month 24 (mean [SD] change at month 24 [n=8]: -1.8 [3.1]; MCID -1).

Conclusion: Adults 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, pain experience, and overall health status. These results demonstrate the broad clinical benefits of exa-cel in patients with SCD.

Disclosures: Sharma: Sangamo Therapeutics: Consultancy; Vertex Pharmaceuticals: Consultancy, Other: Clinical Trial Site PI; Medexus Inc: Consultancy; Editas Medicine: Consultancy; CRISPR Therapeutics: Other: Clinical Trial Site PI, Research Funding; RCI BMT/NMDP: Honoraria, Other: Clinical Trial Medical Monitor. Frangoul: Rocket Pharmaceuticals: Consultancy, Other: Member of DSMB for a study; Jazz Pharmaceuticals: Speakers Bureau; Editas Medicine: Consultancy; Vertex Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Imren: Vertex Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Li: Vertex Pharmaceuticals: Current Employment. Liu: Vertex Pharmaceuticals: Current Employment. Rubin: Vertex Pharmaceuticals: Current Employment. Shi: Vertex Pharmaceuticals: Current Employment. Hobbs: Vertex Pharmaceuticals: Current Employment. Grupp: Adaptimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vertex: Consultancy, Research Funding; Cabaletta: Consultancy, Membership on an entity's Board of Directors or advisory committees; CBMG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Kite: Research Funding; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellectis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH