ASH20: CRISPR, Vertex's gene-editing therapy shows promise in beta thalassaemia, sickle-cell disease

CRISPR Therapeutics and Vertex Pharmaceuticals announced new data showing that 10 patients given the investigational CRISPR/Cas9-based gene-editing therapy CTX001 had a "consistent and sustained response" to treatment. The findings come from two Phase I/II trials and build on results disclosed last month from seven patients with transfusion-dependent beta thalassaemia (TDT) or severe sickle-cell disease (SCD).

Lead investigator Haydar Frangoul remarked "our vision with this approach is to use the patient's own stem cells to provide a transformative treatment," adding "with these data in 10 patients, we can see the potential to fulfill this vision." CTX001 is being investigated in the ongoing studies as a potential one-time curative therapy for patients suffering from TDT and severe SCD.

All TDT patients transfusion independent

CRISPR Therapeutics and Vertex noted that a total of 13 patients with TDT have so far been dosed with CTX001 in the CLIMB-111 trial, with initial safety and efficacy data available on seven subjects who had reached at least three months of follow-up. The results, which were presented at the American Society of Hematology (ASH) meeting, showed that all seven patients had "a similar pattern" of response, with rapid and sustained increases in total haemoglobin, foetal haemoglobin and transfusion independence.

The companies said that all seven patients were transfusion independent with follow-up ranging from three to 18 months after CTX001 infusion, with normal to near normal total haemoglobin levels at last visit, including total haemoglobin from 9.7 g/dL to 14.1 g/dL and foetal haemoglobin from 40.9% to 97.7%. Meanwhile, bone marrow allelic editing data collected from four patients with six months of follow-up and from one patient with 12 months of follow-up demonstrated "a durable effect."

With regard to safety, CRISPR Therapeutics and Vertex said there were four serious adverse events (SAEs) considered related or possibly related to CTX001 in one patient, which all occurred in the context of haemophagocytic lymphohistiocytosis (HLH) and have resolved.

All severe SCD patients remained VOC free

In an update to the CLIMB-121 trial, the companies noted that six patients with SCD have so far been dosed with CTX001, with initial safety and efficacy data available on three subjects who had reached at least three months of follow-up. Results demonstrated that all three patients showed "a similar pattern" of response, with rapid and sustained increases in total haemoglobin and foetal haemoglobin, as well as elimination of vaso-occlusive crises (VOCs).

The data showed that all three patients remained VOC free with follow-up ranging from three to 15 months and had haemoglobin levels in the normal to near normal range, including total haemoglobin from 11.5 g/dL to 13.2 g/dL and foetal haemoglobin levels from 31.3% to 48.0%. Further, bone marrow allelic editing data collected from one patient with six months of follow-up and from one patient with 12 months of follow-up demonstrated "a durable effect."

CRISPR Therapeutics and Vertex indicated that 19 patients have now been dosed with CTX001 across both programmes. Both the CLIMB-111 and CLIMB-121 studies are designed to enrol up to 45 patients, who will be followed for approximately two years after infusion.

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