Novel investigational gene-editing therapy for TDT and SCD

The investigational agent BRL-101 was associated with a manageable safety profile, durable efficacy, and improvements in quality-of-life in patients with either transfusion-dependent thalassaemia (TDT) or sickle cell disease (SCD).

BRL-101 is a gene-editing autologous haematopoietic stem and progenitor cell product. Dr Biao Zheng (BRL Medicine Inc., China) presented the results of 3 single-arm clinical studies (NCT05577312; NCT04211480; NCT04205435) that assessed this agent in patients with TDT (n=15) or SCD (n=1) [1]. Participants underwent myeloablative conditioning with busulfan before receiving a single-dose infusion with BRL-101.

The median follow-up duration was 24.1 months for participants with TDT and 95 days for participants with SCD. All participants with TDT achieved transfusion independence, defined as a 60-day washout period after the last red-cell transfusion, without routine transfusions, and a total Hb level continued ≥9 g/dL. The median time to transfusion independence was 89 days. Moreover, the median duration of transfusion independence was 25.8 months (See Figure). Dr Zheng mentioned that total Hb levels had increased to an average of 12.4 g/dL at 6 months. Regarding the participant with SCD, their Hb level was 7.3 g/dL at baseline and increased to 12.8 g/dL at 2 months; the foetal Hb level was 4.6% at baseline and increased to 64.1% at 3 months.

Figure: Transfusion independence duration exceeding 12 months in all patients with TDT [1]



IIT, investigator-initiated trial; IND, investigational new drug; mL/kg/yr, millilitres per kilogram per year; RBC, red blood cell; TI, transfusion independence; Mo, months; Hb, haemoglobin; g/L, grams per litre.

The researchers noted 5 serious adverse events in the TDT group, namely a decreased platelet count, shock, febrile infection, soft tissue infection, and veno-occlusive liver disease. “Only the decreased platelet count could be attributed to treatment with BRL-101,” stated Dr Zheng. The participant with SCD did not experience any serious adverse events.

Thus, a one-time infusion of BRL-101 delivered encouraging results in patients with TDT and a patient with SCD, supporting further evaluation of this innovative gene-editing therapy.

1. Zheng B, et al. Efficacy and safety of BRL-101 in TDT and SCD. S290, EHA2025 Congress, 12–15 June, Milan, Italy.

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Posted on 2 September 20252 September 2025