Worlds first gene therapy based on the innovative gene-editing tool CRISPR, authorised in the UK

On 16 November 2023, the UK MHRA MHRA authorised the world-first gene therapy based on the innovative gene-editing tool CRISPR.

This post is an attempt to provide brief information on the product and the CRISPR-Cas9 system.

What is the name of the authorised medicine?1

The name of the authorised medicine is:

Casgevy 4-13 × 106 cells/mL dispersion for infusion

Each patient-specific vial of Casgevy contains exagamglogene autotemcel at a batch dependent concentration of genetically modified autologous CD34+ cell enriched population.

Clinical trials1

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.  

It should be stressed that at the time of writing this post, the trials for use of the product in both indications are ongoing.

Licensing route2

In the U.K., Casgevy, was granted an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the MHRA, and Vertex is already working closely with national health authorities to secure access for eligible patients as quickly as possible.

What are the indications of the product?1
  1. Transfusion-dependent β-thalassemia
  2. Sickle cell disease

You can read more about the product in the Summary of Product characteristics (SmPC) and Patient Information Leaflet (PIL) available here.

More about both indications1

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.

Sickle cell disease

Sickle cell disease is particularly common in people with an African or Caribbean family background.

In people with sickle cell disease, this genetic error can lead to attacks of very severe pain, serious and life-threatening infections, and anaemia (whereby your body has difficulty carrying oxygen). 


β-thalassemia mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin. 

In people with β-thalassaemia, it can lead to severe anaemia. Patients often need a blood transfusion every 3 to 5 weeks, and injections and medicines throughout their lives. 

How does Casgevy work?1

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. 

What is CRISPR-Cas9 system and how does it work?

CRISPR is a revolutionary gene-editing technology that allows scientists to make precise changes to an organism’s DNA. It is based on a natural process used by bacteria to defend against viruses.

The acronym CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats.

The CRISPR-Cas9 system consists of two components: a Cas9 protein (a nuclease enzyme) which can cut DNA and a guide RNA (gRNA) that can recognise the sequence of DNA to be edited.

  • To use the CRISPR-Cas9 system the sequence of the genome that is causing a health problem is first identified.3
  • Then, a specific gRNA is created to recognise that particular DNA sequence.
  • The gRNA is attached to the DNA cutting enzyme, Cas9.3
  • The complex is then introduced to the target cells.3
  • It locates the target DNA sequence and cuts it.3
  • At this point, the existing genome can be edited by modifying, deleting or inserting new sequences.3

To develop a better understanding of how the CRISPR-Cas9 system works by watching this clip from the Mayo Clinic or this one from the National Institutes of Health.

Further reading

1.What’s Next For Gene-Editing Darling Crispr After Its ‘Historic’ First-Ever Approval? -29 Nov 2023, Allison Gatlin,

2. What are genome editing and CRISPR-Cas9? – Medline Plus

3. CRISPR-Cas technology –

  1. MHRA
  2. CRISPR explained. Clip by Mayo clinic