Clinical application of base editing for treating β-thalassaemia

Area of Science:

• Hematology
• Gene Therapy
• Clinical Trials

Background:

• Beta-thalassaemia results from reduced or absent beta-haemoglobin production.
• Previous studies explored lab-scale electroporation to modify patient cells.
• The goal was to reactivate fetal haemoglobin (HbF) production.

Purpose of the Study:

• To evaluate the safety and efficacy of CS-101, a transformer base editor therapy, in a Phase 1 clinical trial.
• To assess the potential for CS-101 to restore normal haemoglobin levels in patients with beta-thalassaemia.

Main Methods:

• Conducted a Phase 1 clinical trial (NCT06024876) with five patients.
• Administered autologous CD34+ cells modified with a clinical-scale transformer base editor (CS-101).
• Monitored engraftment times, transfusion needs, haemoglobin levels, and adverse events.

Main Results:

• Median follow-up of 23 months post-infusion.
• All patients stopped red blood cell transfusions, with a median time to last transfusion of 18 days.
• Achieved rapid hematopoietic reconstitution with sustained increases in total haemoglobin and HbF levels.

Conclusions:

• CS-101 demonstrates potential for rapid and sustained increases in haemoglobin and HbF.
• The therapy led to early and enduring transfusion independence in beta-thalassaemia patients.
• Adverse events were consistent with standard stem cell transplantation procedures.