Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia
Year: 2026
Type: article
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.
Source: Blood
Authors: Janet L. Kwiatkowski, Alexis A. Thompson, Jennifer Schneiderman, Isabelle Thuret, Andreas E. Kulozik, Evangelia Yannaki, Marina Cavazzana, Suradej Hongeng, Timothy S. Olson, Martin G. Sauer, Adrian J. Thrasher, Ashutosh Lal, John E. J. Rasko, Joachim B. Kunz, Melissa A. Kinney, Anjulika Chawla, Shamshad Ali, Ge Tao, Himal L. Thakar, Clark Paramore, Niki Witthuhn, Mark C. Walters, Franco Locatelli
Institutions: Children's Hospital of Philadelphia, University of Pennsylvania, Northwestern University, Lurie Children's Hospital, Hôpital de la Timone, German Cancer Research Center, Heidelberg University, G. Papanikolaou General Hospital, Hôpital Necker-Enfants Malades, Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Institut des Maladies Génétiques Imagine, Mahidol University, Ramathibodi Hospital, Medizinische Hochschule Hannover, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London, UCSF Benioff Children's Hospital, Royal Prince Alfred Hospital, University Hospital Heidelberg, Università Cattolica del Sacro Cuore, Bambino Gesù Children's Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
OpenAlex ID: W7123350626