Medicine

Gene Therapy Effective In Beta-Thalassemia, Reduces Need For Transfusion: NEJM

• byDoctor News Daily Team
• 18 February, 2025
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USA: A phase III study showed betibeglogene autotemcel (beti-cel) gene therapy to be safe and effective in patients with non-β0/β0 genotype β-thalassemia.
The study, published in the New England Journal of Medicine, found that treatment with the gene therapy led to a sustained HbAT87Q level and a total hemoglobin level that was high enough to allow transfusion independence in the study population, including those younger than 12 years of age.
Beti-cel gene therapy contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (βA-T87Q) gene. Franco Locatelli and the team aimed to evaluate its safety and efficacy in adult and pediatric patients with transfusion-dependent β-thalassemia and a non–β0/β0 genotype.
For this purpose, 23 patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously. They were followed for a median of 29.5 months.
The primary endpoint was transfusion independence defined as weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months.
The study revealed the following findings:
Transfusion independence occurred in 20 of 22 patients who could be evaluated (91%), including 6 of 7 patients (86%) who were younger than 12 years of age.
The average hemoglobin level during transfusion independence was 11.7 g per deciliter.
Twelve months after beti-cel infusion, the median level of gene therapy–derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) was 8.7 g per deciliter in patients who had transfusion independence.
The safety profile of beti-cel was consistent with that of busulfan-based myeloablation.
Four patients had at least one adverse event that was considered by the investigators to be related or possibly related to beti-cel; all events were nonserious except for thrombocytopenia (in 1 patient).
No cases of cancer were observed.
To conclude, treatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non–β0/β0 genotype, including those younger than 12 years of age.
Reference:
The study titled, "Betibeglogene Autotemcel Gene Therapy for Non–β0/β0 Genotype β-Thalassemia," was published in the New England Journal of Medicine.
DOI: https://www.nejm.org/doi/full/10.1056/NEJMoa2113206