CRISPR, Vertex unveil data for gene-editing therapy in severe haemoglobinopathies

CRISPR Therapeutics and Vertex Pharmaceuticals on Wednesday said data in seven patients from two ongoing Phase I/II trials of CTX001 in severe haemoglobinopathies will be presented at the upcoming American Society of Hematology (ASH) meeting next month. The companies noted that the experimental autologous CRISPR/Cas9 gene-editing therapy is being investigated in these two ongoing studies as a potential one-time curative treatment for patients suffering from transfusion-dependent beta thalassaemia (TDT) and severe sickle-cell disease (SCD).

The treatment involves engineering a patient's haematopoietic stem cells to produce high levels of foetal haemoglobin (HbF) in red blood cells. CRISPR and Vertex explained that the "elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients, and reduce painful and debilitating sickle crises for SCD patients." The ASH presentations will include at least three months of follow-up from five TDT patients after CTX001 infusion in the CLIMB-111 trial, as well as from two severe SCD patients in the CLIMB-121 study.

According to an abstract posted online ahead of the ASH meeting, all patients demonstrated increases in total haemoglobin and HbF over time. Researchers noted that the first patient with TDT who received CTX001 has remained transfusion-free for over 15 months. Meanwhile, neither of the SCD patients have experienced vaso-occlusive crises (VOCs) since CTX001 infusion, while the first of these has remained free of VOCs for over a year.

In regards to safety, researchers said that in all seven patients included in the analysis, CTX001 infusion was generally consistent with busulfan myeloablation. However, four serious adverse events (SAEs) potentially related to the treatment were reported in one of the TDT patients, including headache, haemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome and idiopathic pneumonia syndrome. All of the SAEs occurred in the context of HLH and were either resolved or clinically improving at the time of this analysis, researchers noted.

The study authors concluded that these early findings "demonstrate that CTX001 is a potential functional cure for the treatment of TDT and SCD."

In October, CRISPR unveiled top-line results from a Phase I trial showing early evidence of anti-tumour activity with CTX110, the company's allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies.

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