In late 2023, the Medicines and Healthcare Products Regulatory Agency (MHRA) approved Vertex Pharmaceuticals’ Casgevy (exagamglogene autotemcel) for sickle cell disease (SCD), marking the world’s first clustered regularly interspaced short palindromic repeats (CRISPR)-based approval. Last month, the National Institute for Health and Care Excellence (NICE) endorsed Casgevy for use in the National Health Service (NHS) under a managed access scheme, recognising its significant benefits over current treatments and potential to address health inequalities.
SCD is a life-threatening disease that affects approximately 15,000 people in the UK. It is caused by mutations to the haemoglobin gene, resulting in rigid red blood cells that block blood flow. A main SCD symptom is vaso-occlusive crises (VOCs), where the restriction of blood flow leads to tissue ischemia, requiring hospitalisation and pain management strategies.
In total, the MHRA has approved five products for SCD. The first drug in the UK was Theravia’s small molecule Siklos (hydroxyurea) in 2007. This was followed by the first biologic approval, Novartis’ monoclonal antibody Adakveo (crizanlizumab) in 2020.
Casgevy was the second biologic and most recent product to receive MHRA approval for SCD, in November 2023. So far, it is the only CRISPR-based product on the global market. Casgevy works by editing the faulty gene in a patient’s bone marrow stem cell, enabling the production of functional haemoglobin. Taking into account the clinical and cost-effectiveness of Casgevy, NICE has since recommended this product for use in the NHS for patients with severe forms of SCD.
The SCD products that were available before Casgevy focused on symptom management, such as reducing the frequency of VOCs. In comparison, Casgevy offers a potential curative option for SCD via gene editing. Until now, the only other curative option was a stem cell transplant, which requires a closely matched donor and carries a plethora of risks. There are additional issues with prior SCD treatments such as efficacy, as two of the five products to have received MHRA approval were later withdrawn from the UK market. This includes Adakveo, which was pulled from the UK last year after failing to demonstrate a significant reduction in the number of painful crises in SCD patients.
In addition to being a potential cure for SCD, Casgevy demonstrated a great reduction and elimination of VOCs in clinical trials. By preventing these events, Casgevy treatment leads to fewer hospital admissions for SCD patients, proving beneficial for health services and vastly improving patients’ quality of life.
A key factor in NICE’s decision was the potential for Casgevy to reduce health inequalities. SCD disproportionately affects people from African, Caribbean, Middle Eastern, or South Asian backgrounds. By making this potentially curative treatment available through the NHS, the UK is taking a significant step to narrow the gap in healthcare disparities for these communities.
Still, Casgevy is a complex, one-off treatment that requires personalized stem cell collection, modification, and transplantation. As such, the listed price for a single dose of Casgevy is £1.65m ($2.09m). However, following a commercial agreement, the product has been made available to the NHS at a discount. NICE has recommended Casgevy under a managed access scheme. This scheme enables further data collection regarding the utility and cost-effectiveness of Casgevy, which may result in more routine NHS use.
By recommending Casgevy for use in the NHS in England, NICE has considered the potential impact this product may have in terms of providing an efficacious, curative treatment for SCD patients that may also reduce health inequalities. NICE’s endorsement of Casgevy represents a monumental advancement in the accessibility of this potential SCD cure, signaling the start of a new era of gene modifying therapies, and offering hope to thousands of patients.
