Title: Voxelotor for treating haemolytic anaemia in people with sickle cell disease [ID1403]
Funder: Department of Health and Social Care

Abstract: Sickle cell disease is the name given to a group of lifelong inherited conditions that affect haemoglobin. The most common and often severe type of sickle cell disease occurs when people inherit a copy of the beta globin gene with the sickle mutation from both parents (homozygous sickle cell anaemia). Heterozygous sickle cell anaemia occurs when people inherit one copy of the beta globin gene with the sickle mutation from one parent and a different variant of the beta globin gene from the other parent. In all cases, the abnormal haemoglobin, known as haemoglobin S, tends to form polymers (or chains) with other haemoglobin S molecules. These polymers cause red blood cells to become rigid and misshapen, resembling a crescent (or sickle).[1] _x000D_ _x000D_ Sickle-shaped red blood cells do not last as long in the body as regular shaped round red blood cells and get broken down more readily in a process known as haemolysis.[2] People with sickle cell disease often have anaemia because too much haemolysis occurs and there are not enough red blood cells to carry oxygen throughout the body. Sickle-shaped red blood cells also do not flow easily through blood vessels and bond abnormally with other blood cells and blood vessel walls which can cause blockages.[2] This may lead to insufficient oxygen being delivered to tissues, causing ischaemic injuries and excruciating pain (known as acute sickle cell crises). Chronic complications caused by anaemia and sickle cell crises include progressive organ damage, fatigue and shortness of breath. Acute complications may also include acute chest syndrome and stroke.[1] _x000D_ _x000D_ It is estimated that there are 15,000 people with sickle cell disease in England.[3] The prevalence of sickle cell disease varies considerably across different ethnic communities, mainly affecting people of African or African-Caribbean family background, although the sickle gene is found in all ethnic groups.[4] The prevalence of the disease is increasing because of immigration into the UK, new births and increased survival.[5]_x000D_ _x000D_ Sickle cell disease causes significant morbidity and mortality and usually requires lifelong treatment. Management in England focuses on reducing the chances of experiencing a sickle cell crisis by avoiding dehydration, sudden changes in temperature and infection. Sickle cell crises may be extremely painful and will often require emergency admission to hospital and pain management with paracetamol, non-steroidal anti-inflammatory drugs and opiates. Hydroxycarbamide can also be used to increase the production of foetal haemoglobin, which improves blood cell hydration and reduces red blood cell adhesion. This can reduce both acute painful crises and acute chest syndrome (caused by reduced blood flow in the lungs) in people with recurrent painful crises. Blood transfusions including exchange transfusions (where sickle red blood cells are replaced with healthy red blood cells) and simple (top-up) transfusions can help to maintain a healthy proportion of normal red blood cells to sickle red blood cells. Allogenic stem cell transplants may be considered but are not done often because of the significant risks involved.[6]_x000D_ _x000D_ References_x000D_ 1. Nevitt SJ, Jones AP, Howard J. Hydroxyurea (hydroxycarbamide) for sickle cell disease. Cochrane Database of Systematic Reviews 2017, Issue 4_x000D_ 2. Kato et al. 2018; Sickle cell disease, Nature Reviews Disease Primers; 4, 18010_x000D_ 3. NHS England (2018/2019) NHS manual for prescribed specialist services (2018/2019) (Accessed June 2021)_x000D_ 4. Clinical Knowledge (2016) Sickle cell disease: prevalence (Accessed June 2021)_x000D_ 5. NHS sickle cell and thalassaemia (SCT) screening programme (Accessed June 2021)_x000D_ 6. NHS, Sickle cell disease: treatment (Accessed June 2021)

Lay abstract: To appraise the clinical and cost effectiveness of voxelotor within its marketing authorisation for treating haemolytic anaemia in people with sickle cell disease.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: BLOOD