The therapy, exagamglogene autotemcel (exa-cel), has been developed for the treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). The submission is supported by two global Phase 3 studies.
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa-cel represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing, and commercialization of exa-cel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.
Last autumn, Vertex flagged that it had completed discussions with the EMA on the data needed to support the marketing applications and that it was on track to submit that by the end of 2022. If approved, exa-cel will become the first CRISPR therapy to achieve regulatory approval for a genetic disease.
In August 2022, the US Food and Drug Administration (FDA) approved bluebird bio’s Zynteglo, a gene therapy for beta-thalassemia, marking the first US approval for a lentiviral vector.
While Zynteglo was given the green light in Europe in 2019, the company took the drug off the market as part of its withdrawal from the region after failing to reach agreements with governments over coverage, turning its attention to the US instead.
How it works
Formerly known as CTX001, exa-cel is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with SCD or TDT, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF) in red blood cells. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating vaso-occlusive crises for patients with SCD and alleviate transfusion requirements for patients with TDT, say the developers.
Exa-cel has been granted Orphan Drug Designation from the EU Commission, as well as Priority Medicines (PRIME) designation for both SCD and TDT from the EMA. Vertex has also begun the rolling Biologics License Application (BLA) submission to the US FDA and said that it expects to complete that application by the end of the first quarter this year.