TOP STORY | EMA Validates Vertex’s/CRISPR Submission Of Exa-Cel For β-Τhal And SCD

A significant step forward towards a landmark approval in the EU was taken yesterday, 25 January 2023, with Vertex and CRISPR Therapeutics obtaining validation by the European Medicines Agency (EMA) of their approval application for the gene-edited therapy exa-cel.


The Marketing Authorization Application (MAA) for exagamglogene autotemcel (exa-cel), marks the first regulatory submission in the EU for a CRISPR-based medicine.

Through the validation, exa-cel is indicated for the treatment of transfusion-dependent β-thalassaemia (TDT) and sickle cell disease (SCD). In addition, the validation confirms that all of the elements needed for exa-cel’s scientific assessment are present.

It is noted that exa-cel has PRIME designation from the EMA, making it eligible for a priority review that usually takes 150 days, rather than the typical 210 days. The timeline suggests exa-cel could win approval in Europe later this year and become the first marketed CRISPR-Cas9 treatment.

Vertex has also begun the rolling Biologics License Application (BLA) submission to the US Food and Drug Administration (FDA) and expects to complete the BLA by the end of the first quarter.

How does exa-cel work?

Exa-cel, formerly known as CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy. The therapy works by editing a patient’s own hematopoietic stem cells to produce high levels of fetal haemoglobin (HbF; haemoglobin F) in red blood cells. The edited cells, exa-cel, are then infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT). One-time treatment with exa-cel has freed patients from blood transfusions and vaso-occlusive crises.

The challenges ahead

History shows approval could be just the start of the challenges Vertex and CRISPR will be facing in Europe. The companies are following in the footsteps of bluebird bio, which won conditional EMA approval for its autologous lentiviral gene therapy, Zynteglo, for β-thalassaemia in 2019, only to retreat from the market two years later,  after failing to reach an agreement with European payers on reimbursement for its gene therapy.

This gives Vertex and CRISPR a clear advantage at the market opportunity for a potentially curative treatment of β-thalassaemia, which is more common in Europe than the U.S., and sickle cell. But it also shows how Europe’s fragmented payer landscape can be a hostile environment to expensive, advanced therapies.

How might the region get back on track? For the first time in a generation, the EU will revise its Pharmaceuticals Legislation – the European Commission’s proposal is expected in the first quarter of 2023. The initiative aims to balance affordability and access, among other concerns, and will play a large role in whether European patients will have access to ATMPs for years to come.

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