In a groundbreaking move, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization for CASGEVY™ (exagamglogene autotemcel [exa-cel]), marking the first regulatory approval for a CRISPR-based gene-editing therapy globally. Developed by Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics, CASGEVY is designed to treat sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).
CASGEVY is indicated for patients aged 12 and older with SCD experiencing recurrent vaso-occlusive crises (VOCs) or TDT, where a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor is unavailable. The therapy represents a beacon of hope for approximately 2,000 eligible patients in the UK.
Vertex’s Chief Executive Officer and President, Reshma Kewalramani, expressed the significance of this milestone, stating, “Today is a historic day in science and medicine: this authorization of CASGEVY in Great Britain is the first regulatory authorization of a CRISPR-based therapy in the world.”
CASGEVY’s approval is based on successful outcomes from global clinical trials in SCD and TDT, where patients achieved freedom from severe VOCs or transfusion independence for at least 12 consecutive months. The safety profile of CASGEVY, administered through myeloablative conditioning with busulfan and hematopoietic stem cell transplant, remains consistent with expectations.
Professor Josu de la Fuente, Principal Investigator in the CLIMB-111 and CLIMB-121 studies, highlighted the significance of this authorization in offering a new treatment option for eligible patients and expressed eagerness for swift patient access.
CASGEVY, known as exa-cel in the UK, received an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the MHRA. Vertex is actively collaborating with national health authorities to expedite access for eligible patients.
About Sickle Cell Disease and Beta Thalassemia
Sickle cell disease (SCD) is an inherited blood disorder causing misshapen or “sickled” blood cells, leading to severe pain, organ damage, and shortened lifespan. Beta thalassemia is another inherited blood disorder resulting in anemia, fatigue, and complications such as an enlarged spleen and misshapen bones.
Current treatments for these conditions are largely symptomatic, and a stem cell transplant from a matched donor offers the only cure. However, this option is limited to a small fraction of patients. CASGEVY represents a promising advancement in providing a more accessible and effective treatment option.
CASGEVY: A Game-Changer in Gene Editing
CASGEVY is a genetically modified autologous CD34+ cell enriched population, edited ex vivo by CRISPR/Cas9 at the erythroid-specific enhancer region of the BCL11A gene. The therapy demonstrated positive outcomes in pivotal trials, and its safety and efficacy are now under review by regulatory bodies globally.
The UK’s approval sets a precedent for other nations in adopting CRISPR-based therapies for genetic disorders. The US Food and Drug Administration (FDA) has granted Priority Review for SCD and Standard Review for TDT, with target action dates in December 2023 and March 2024, respectively.
Conditional Marketing Authorizations and Future Prospects
Conditional marketing authorizations (CMAs) are granted for medicines addressing significant unmet medical needs. CASGEVY’s CMA is valid for one year, renewable annually with ongoing regulatory data review.
Vertex and CRISPR’s collaboration, initiated in 2015, focuses on leveraging CRISPR/Cas9 for developing treatments addressing genetic causes of human diseases. The success of CASGEVY underscores the potential of this partnership in delivering innovative therapies.
The UK’s regulatory agility in approving groundbreaking therapies reflects a broader commitment to accelerating access to novel treatments. CASGEVY’s approval for SCD and TDT marks a transformative moment in the landscape of gene-editing therapies, offering hope to patients worldwide.
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