The Medicines and Healthcare products Regulatory Agency (MHRA) has granted authorisation to a ‘world-first’ gene therapy that aims to cure sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT) in patients aged 12 and over.
Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel) is now the first licensed treatment that uses the gene-editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020.
SCD and beta-thalassaemia are both genetic conditions caused by errors in the genes for haemoglobin, which is used by red blood cells to carry oxygen around the body.
For those with SCD, this genetic error can lead to attacks of very severe pain known as vaso-occlusive crises (VOCs), serious and life-threatening infections and anaemia, while in beta-thalassaemia, it can lead to severe anaemia, and patients often require regular blood transfusions throughout their lives.
Casgevy, which is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin, has been specifically authorised for use in SCD patients with recurrent VOCs or those with TDT for whom a human leukocyte antigen matched related haematopoietic stem cell donor is not available.
The UK regulator’s decision was supported by two global clinical trials of Casgevy in SCD and TDT, which met their respective primary outcomes of becoming free from severe VOCs or transfusion independent for at least 12 consecutive months.
Julian Beach, interim executive director of healthcare quality and access at the MHRA, said: “Both SCD and beta-thalassaemia are painful, life-long conditions that in some cases can be fatal. To date, a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection – has been the only permanent treatment option.”
Beach added that the MHRA will “continue to closely monitor the safety and effectiveness of Casgevy” through real-world safety data and post-authorisation safety studies.
Casgevy is the first treatment to emerge from Vertex and CRISPR Therapeutics’ strategic partnership, which was originally announced in 2015. Vertex now leads the global development, manufacturing and commercialisation of Casgevy and splits programme costs and profits worldwide with CRISPR.
The companies have welcomed the MHRA’s decision, with Samarth Kulkarni, chairman and chief executive officer of CRISPR Therapeutics, stating: “I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases.”