The Medicines and Healthcare products Regulatory Agency (MHRA) has authorised the world’s first gene therapy for sickle-cell disease (SCD) and transfusion-dependent β-thalassemia (TDT).
Casgevy (exagamglogene autotemcel, or exa-cel) is the first medicine to be licensed that uses gene editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020.
The treatment from Vertex and CRISPR Therapeutics is still under review by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) though decisions are expected this year.
“Today is a historic day in science and medicine: this authorisation of Casgevy in Great Britain is the first regulatory authorisation of a CRISPR-based therapy in the world,” said Reshma Kewalramani, Chief Executive Officer and President of Vertex.
First of its kind treatment
The therapy has been authorised for the treatment of eligible patients 12 years of age and older with SCD with recurrent vaso-occlusive crises (VOCs) or TDT, for whom a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor is not available. It is estimated that this includes around 2,000 patients in the UK.
Both sickle cell disease and β-thalassemia are genetic conditions caused by errors in the genes for haemoglobin, which is used by red blood cells to carry oxygen around the body.
Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long.
Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA said: “Both sickle cell disease and β-thalassemia 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.
“I am pleased to announce that we have authorised an innovative and first-of-its-kind gene-editing treatment called Casgevy, which in trials has been found to restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent β -thalassaemia, relieving the symptoms of disease.”
Trial results for Casgevy
The authorisation is based on positive clinical trial data. In the clinical trial for sickle-cell disease, 45 patients have currently received Casgevy but only 29 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these eligible patients, 28 (97%) were free of severe pain crises for at least 12 months after treatment.
In the clinical trial for transfusion-dependent β-thalassemia, 54 patients have currently received Casgevy but only 42 patients have been in the trial long enough to be eligible for the primary efficacy interim analysis. Of these, 39 (93%) did not need a red blood cell transfusion for at least 12 months after treatment. The remaining three had more than a 70% reduction in the need for red cell transfusions.
Side effects from treatment were similar to those associated with autologous stem cell transplants, including nausea, fatigue, fever and increased risk of infection. No significant safety concerns were identified during the trials.
“I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases,” said Samarth Kulkarni, Chairman and Chief Executive Officer of CRISPR Therapeutics.”
Diana Spencer, Senior Digital Content Editor, DDW
