Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia
1
Issued Date
2026-01-01
Resource Type
ISSN
00064971
eISSN
15280020
Scopus ID
2-s2.0-105035232567
Pubmed ID
41525466
Journal Title
Blood
Rights Holder(s)
SCOPUS
Bibliographic Citation
Blood (2026)
Suggested Citation
Kwiatkowski J.L., Thompson A.A., Schneiderman J., Thuret I., Kulozik A.E., Yannaki E., Cavazzana M., Hongeng S., Olson T.S., Sauer M.G., Thrasher A.J., Lal A., Rasko J.E.J., Kunz J.B., Kinney M.A., Chawla A., Ali S., Tao G., Thakar H.L., Paramore C., Witthuhn N., Walters M.C., Locatelli F. Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia. Blood (2026). doi:10.1182/blood.2025029196 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116212
Title
Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia
Author's Affiliation
Inserm
Université Paris Cité
University of Pennsylvania Perelman School of Medicine
Northwestern University Feinberg School of Medicine
Hannover Medical School
The Children's Hospital of Philadelphia
Università Cattolica del Sacro Cuore, Campus di Roma
German Cancer Research Center
Universitätsklinikum Heidelberg
UCL Great Ormond Street Institute of Child Health
Royal Prince Alfred Hospital
Hopital La Timone
IRCCS Ospedale Pediatrico Bambino Gesù
Ramathibodi Hospital
l'Institut des Maladies Génétiques Imagine
UCSF Benioff Children's Hospital Oakland
George Papanicolaou General Hospital
Genetix Biotherapeutics
Université Paris Cité
University of Pennsylvania Perelman School of Medicine
Northwestern University Feinberg School of Medicine
Hannover Medical School
The Children's Hospital of Philadelphia
Università Cattolica del Sacro Cuore, Campus di Roma
German Cancer Research Center
Universitätsklinikum Heidelberg
UCL Great Ormond Street Institute of Child Health
Royal Prince Alfred Hospital
Hopital La Timone
IRCCS Ospedale Pediatrico Bambino Gesù
Ramathibodi Hospital
l'Institut des Maladies Génétiques Imagine
UCSF Benioff Children's Hospital Oakland
George Papanicolaou General Hospital
Genetix Biotherapeutics
Corresponding Author(s)
Other Contributor(s)
Abstract
Abstract: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia (TDT) involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a modified β-globin gene to produce functional adult hemoglobin (Hb) containing βA-T87Q-globin (HbAT87Q). Sixty-three participants with TDT (median age, 17 years [range, 4-35]) received beti-cel in phase 1/2 (n = 22) or phase 3 (n = 41) studies and enrolled in the long-term follow-up LTF-303 study (median follow-up, 5.9 years [range, 2.9-10.1]). Manufacturing refinements in phase 3 increased transduction efficiency, resulting in higher drug product vector copy number and HbAT87Q levels, which translated into higher Hb and transfusion independence (TI) rates than in phase 1/2. TI was achieved by 15 of 22 (68.2%) phase 1/2 participants (median weighted average Hb during TI, 10.2 g/dL) and 37 of 41 (90.2%) of phase 3 participants (median, 11.2 g/dL), and was sustained through last follow-up. Treatment efficacy was similar across ages and TDT genotypes. Among participants achieving TI, 38 of 52 (73%) had discontinued iron chelation at last follow-up, with no increase in liver iron concentration. Markers of ineffective erythropoiesis, including serum transferrin receptor and erythropoietin, improved with restoration of iron homeostasis. Health-related quality-of-life assessment scores showed durable improvements. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. These findings establish beti-cel as a durable, 1-time therapy that achieves TI, restores iron balance, and improves quality of life, offering a potentially curative treatment option for people with TDT. This trial was registered at www.clinicaltrials.gov as NCT02633943.