EHA24: Vertex showcases Casgevy's long-term benefits in blood disorders

Vertex Pharmaceuticals has revealed promising long-term clinical trial data for its CRISPR-based gene-editing therapy, Casgevy (exagamglogene autotemcel), demonstrating "consistent and durable" benefits for patients suffering from severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The findings were showcased at the European Hematology Association (EHA) annual meeting and are expected to bolster the launch momentum for Casgevy, which the FDA approved in December for SCD and later for TDT. The therapy faces competition from bluebird bio's gene therapy, Lyfgenia (lovotibeglogene autotemcel).

The data presented were derived from the CLIMB-111 and CLIMB-121 trials, alongside the CLIMB-131 long-term follow-up study, encompassing more than 100 patients treated with Casgevy. The longest follow-up period now surpasses five years. Vertex reports that the efficacy data align with previously reported primary and key secondary endpoints, showing sustained and stable levels of foetal haemoglobin (HbF) and allelic editing over time.

In the CLIMB-121 trial, 36 out of 39 evaluable SCD patients (92.3%) were free from vaso-occlusive crises (VOCs) for at least 12 consecutive months. On average, these patients remained VOC-free for 27.9 months, with the longest duration extending to 54.8 months. Additionally, 38 patients (97.4%) experienced no VOC-related hospitalisations for a minimum of 12 consecutive months.

For the CLIMB-111 study involving TDT patients, 49 out of 52 evaluable patients (94.2%) achieved transfusion independence for at least 12 consecutive months, with a mean weighted haemoglobin level of at least 9 g/dL. The average duration of transfusion independence was 31 months, with the longest period reaching 59.4 months. Furthermore, all TDT patients with at least 16 months of follow-up are now free from transfusions. In the long-term follow-up study, two out of three patients who initially did not achieve transfusion independence later reached this milestone, while the third patient has been free from transfusions for 3.4 months.

Vertex also noted that for both SCD and TDT cohorts, the edited BCL11A alleles persisted over time in bone marrow and peripheral blood. This persistence indicates successful long-term editing in haematopoietic stem cells. Moreover, all patients achieved successful engraftment of neutrophils and platelets following their Casgevy infusion.

The consistent and durable benefits observed in these trials are a significant milestone for Vertex and its partner CRISPR Therapeutics. The ability of Casgevy to maintain stable levels of HbF and achieve long-term transfusion independence or VOC-free periods points to its potential as a transformative therapy for patients with SCD and TDT. The latest data will likely play a crucial role in securing confidence from the medical community and enhancing the therapy's market adoption.