Sickle cell and beta thalassemia: what are the treatment options and challenges?

DOI: https://doi.org/10.58248/PN754

Sickle cell disorder also referred to as Sickle cell disease(SCD) and beta thalassemia (BT) are inherited blood conditions that reduce life expectancy and quality of life. Both are caused by mutations in a single gene affecting haemoglobin, the protein that carries oxygen in red blood cells. SCD leads to sickle-shaped cells that block blood vessels, causing severe pain and organ damage. BT results in insufficient beta globin chains, leading to life-threatening anaemia that often requires lifelong blood transfusions. These conditions disproportionately affect people of African, Caribbean, South Asian, Mediterranean and Middle Eastern backgrounds. Around 17,500 people in the UK have SCD and 1,000 have BT.

Standard care includes blood transfusions, iron chelation therapy to manage iron overload, and drugs such as hydroxyurea for SCD and luspatercept for BT. Allogeneic stem cell transplantation (bone marrow transplant) is the only established curative option but is limited by donor availability and risks such as graft-versus-host disease. Most patients rely on lifelong symptom management, which can involve frequent hospital visits and complications including organ damage.

Recent advances in personalised medicines, also called precision medicines, offer potential cures. These include advanced therapy medicinal products (ATMPs) such as gene and cell therapies. In 2023, the UK became the first country to approve exa-cel, a CRISPR-Cas9 gene-editing therapy for severe SCD and BT. CRISPR-Cas9 edits the patient’s own stem cells to reactivate fetal haemoglobin production, reducing symptoms and transfusion needs. NICE has recommended exa-cel under a managed access scheme for patients aged 12 or older with severe disease and no suitable donor for conventional transplant. Around 50 patients a year are expected to receive the therapy initially.

Gene therapy delivery requires specialist centres, trained staff and high-dose chemotherapy before treatment. Risks include infertility, infections and possible long-term cancer risk. The upfront cost of exa-cel exceeds £1.5 million per dose, although NHS England has negotiated a commercial deal. Populations most affected by SCD and BT face barriers to care, including shortages of specialist staff and reported racial inequalities. These challenges raise questions about equitable access and the need for culturally competent care.

This briefing was produced in consultation with experts and stakeholders, who are listed at the end of the briefing. POST would like to thank everyone who contributed their expertise to this briefing.