The first CRISPR/Cas9-based therapy has reached the market

The admission of Casgevy (Exagamglogene autotemcel) opens a new chapter in CRISPR/Cas9-based gene therapy and ATMP manufacture
 

Patients in the United Kingdom of Great Britain and Northern Ireland, suffering from sickle cell disease and transfusion-dependent β-Thalassemia, have a new therapeutic option since Nov 16th 2023. The respective national health authority, MHRA, announced the approval of Casgevy (Exagamglogene autotemcel).
 

CRISPR/Cas9 - an ATMP success story

Since its first discovery in the 1980s and realization of its potential for genetic editing in 2010s, the CRISPR/Cas9 system has become a success story. It resulted in a Nobel Prize in Chemistry 2020, faced public attention, and stands apart from other high-fidelity zinc-finger nuclease systems due to its ease of use. Today, a plethora of potential therapeutic applications have come within reach with the CRISPR/Cas9 system.
 

Effectiveness of Casgevy

The therapeutic strategy of Casgevy (Exagamglogene autotemcel) and the approach presented by Vertex Pharmaceuticals can be considered outstanding. It is designed to reactivate an inbuilt, but dormant mechanism, in the patient’s haemoatopoietic stem and progenitor cells, by inducing the production of fetal haemoglobin. For this, such cells are extracted from peripheral blood after mobilization, transduced (gene-edited with the CRISPR/Cas9 system) and autologously reintroduced. Part of the therapy is a myeloablative treatment regime to condition the bone marrow and enhance subsequent therapeutic cell engraftment. The engrafted therapeutic cells give rise to erythrocytes, which then carry fetal heamoglobin. As a result, the lack of intact β-globine, which is associated with the pathophysiology treated in β-thalassemia and sickle cell anemia, can be compensated.

Already 2021, the product’s success was foreshadowed with results presented by Frangoul et al.. It was reflected by a reduced frequency of required blood transfusions of patients after treatment. This is clearly a relevant clinical outcome for concerned patients. As stated in the Summary of Product Characteristics (SmPC), no off-target editing has been observed. The duration of the therapeutic effect, excerted by engrafted cells is not yet clear but might potentially be life-long.

CRISPR/Cas9 as a promising therapy system for the field of ATMP

As seen with Casgevy (Exagamglogene autotemcel), CRISPR/Cas9 based therapies have reached the bedside and the patients therein. With more than 50 investigational new drugs under investigation in various fields of application, it is rather a question of when the next CRISPR/Cas9 based therapies will reach the market.

Valicare can help you with your ATMP

Are you planning an ATMP manufacture to supply your clinical study with clinical samples of CRISPR/Cas9-based therapy? Would you have questions or require support, stirring your ATMP-manufacture towards marketing authorization?

We can support you with custom solutions, tailored to your manufacturing process, along the way.

Please see our cult.tainer® concept for a stand-alone, turnkey-solution for ATMP-manufacture to speed up your ATMP from bench to bedside.

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