- Exagamglogene autotemcel resulted in significant improvements in quality of life for patients with severe sickle cell disease or transfusion-dependent beta-thalassemia.
- Patients reported clinically meaningful improvements in overall quality of life, including physical, social/family, functional, and emotional well-being.
- The gene therapy was previously shown to reduce vaso-occlusive crises in sickle cell disease, and lead to transfusion independence in beta-thalassemia.
Treatment with the gene therapy exagamglogene autotemcel (exa-cel; Casgevy) led to significant improvements in quality of life for patients with severe sickle cell disease or transfusion-dependent beta-thalassemia, data from two phase III trials showed.
Patients with sickle cell disease and transfusion-dependent beta-thalassemia reported clinically meaningful improvements in overall quality of life, including physical, social/family, functional, and emotional well-being, with these improvements beginning as early as 6 months following exa-cel infusion, as noted in the two studies that were published in Blood Advances.
"This treatment has transformed lives and its impact was evident as we followed up with patients in our clinic," said Haydar Frangoul, MD, of the Sarah Cannon Research Institute and TriStar Centennial Children's Hospital in Nashville, Tennessee, who was an author on both studies, in a press release. "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."
A prespecified interim analysis of the sickle cell disease trial, known as CLIMB SCD-121, showed that exa-cel, a one-time ex vivo CRISPR/Cas9 gene-edited cell therapy, eliminated vaso-occlusive crises in 97% of participants with severe sickle cell disease. These results led to exa-cel's FDA approval in December 2023 for patients ages 12 and older with sickle cell disease.
The next month, the FDA expanded exa-cel's approval to include patients ages 12 and older with transfusion-dependent beta thalassemia. A prespecified interim analysis of the CLIMB THAL-111 trial showed that among 54 evaluable patients (those with at least 16 months of follow-up), 53 achieved transfusion independence for at least 12 consecutive months with a weighted average hemoglobin of at least 9 g/dL.
Participants who completed the CLIMB SCD-121 and CLIMB THAL-111 trials were offered to enroll in the 13-year extension study CLIMB-131.
Sickle Cell Disease
Using three quality-of-life assessments and one pain scale for 30 adult patients, and two quality-of-life assessments along with one pain scale for 12 adolescents, Frangoul and colleagues reported that scores across all domains surpassed thresholds for minimal clinically important differences after exa-cell infusion.
For adults, the ASCQ-Me quality-of-life scale -- designed to assess multiple domains of health-related quality of life in adults with sickle cell disease -- showed improvements at 36 months, including:
- Pain impact (mean change from baseline 8.1 points)
- Emotional impact (8.5 points)
- Social functioning impact (16.5 points)
- Stiffness impact (5.1 points)
- Sleep impact (5.7 points)
- Pain episode frequency (-21.0 points)
- Pain episode severity (-5.1 points)
For adolescent patients, the mean change from baseline in PedsQL total score (a measure of health-related quality of life in children or adolescents with chronic diseases) was 23 points by month 6, which was maintained through month 24, with improvements seen across all subcomponents and subscales, including school functioning (+45.0 points), social functioning (+18.3 points), and emotional functioning (+16.7 points).
"Taken together, these results, which represent the largest patient-reported outcome dataset for patients with sickle cell disease following hematopoietic stem cell transplantation or gene therapy, show exa-cel infusion leads to clinically meaningful improvements in quality of life in patients with severe [disease]," Frangoul and colleagues wrote.
Transfusion-Dependent Beta-Thalassemia
Using the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) -- a quantitative measure of overall health through five dimensions of health and ability, adults had a mean score improvement of 14.0 points from a baseline of 82.2 at 48 months after exa-cel infusion, reported Franco Locatelli, MD, PhD, of the IRCCS Ospedale Pediatrico Bambino Gesù in Rome, and colleagues.
For adolescents, the baseline score at infusion was 81.3, with a mean score improvement of 6.1 points at month 24.
For both adults and adolescents, treatment with exa-cel led to clinically meaningful improvements and surpassed thresholds for minimal clinically important differences.
All participants also reported less fatigue following exa-cel infusion.
Disclosures
The CLIMB trials were sponsored by Vertex Pharmaceuticals.
Frangoul has received consulting fees from Vertex Pharmaceuticals, Editas Medicine, and Rocket Pharmaceuticals; honoraria from Jazz Pharmaceuticals; advisory fees from Rocket Pharmaceuticals; and served in a leadership or fiduciary position for Vertex Pharmaceuticals.
Locatelli is on the advisory board for Amgen, Neovii, Novartis, Sanofi, and Vertex, and the speaker's bureau for Amgen, Bluebird Bio, Gilead, Jazz Pharmaceuticals, Medac, Miltenyi, Neovii, Novartis, and SOBI.
Co-authors reported multiple relationships with industry.
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