Title: Sebelipase alfa for treating Wolman disease (rapidly progressive LAL-D) [ID3995]
Funder: Department of Health and Social Care

Abstract: Lysosomal acid lipase (LAL) deficiency is an inherited autosomal recessive lysosomal storage disorder.[1] It is caused by a deficiency of the LAL enzyme resulting in abnormal accumulation of lipids in cells primarily in the gastrointestinal, hepatic and cardiovascular systems. LAL deficiency is caused by a marked decrease or loss in LAL enzyme activity and affects people of all ages from infancy through adulthood. _x000D_ _x000D_ Wolman disease is a type of LAL deficiency that presents in babies and children under 2 years as rapidly progressing multisystem disease. [1] Wolman disease is characterised by intestinal failure and severe malabsorption, growth failure, hepatosplenomegaly and progressive liver fibrosis and cirrhosis. [2],[3] The condition normally results in death in the first 6 months of life, usually due to multiple organ failure. For the smaller group of children diagnosed slightly later (under 2 years), there is still usually evidence of growth failure in the first 6 months of life. [3] _x000D_ _x000D_ Cholesteryl ester storage disease is a type of LAL deficiency presenting later in life, mostly in childhood (over 2 years) and adolescence. [4] It tends to have less severe presenting symptoms but can lead to hepatic and cardiovascular problems including hepatomegaly, cirrhosis, liver failure, dyslipidaemia and accelerated atherosclerosis.[4] _x000D_ _x000D_ The prevalence of LAL deficiency in England is unknown based on currently available information. It is estimated that on average 1 or 2 babies with Wolman disease are born every 1 or 2 years. The estimated incidence rate for Wolman disease is approximately 1 in 350,000 births, and for cholesteryl ester storage disease, it is 2.5 in 100,000 births. [5],[6] LAL deficiency affects males and females equally. _x000D_ _x000D_ Enzyme replacement therapy with sebelipase alfa is the only licensed treatment option for LAL deficiency, including the subgroup with Wolman disease. [1] Currently, sebelipase alfa is not routinely commissioned by NHS England, [7] however most babies and children with Wolman disease are treated with sebelipase alfa through clinical trials or a company compassionate use program. Treatment for Wolman disease without sebelipase alfa is usually palliative and supportive, because of the severe, multiorgan and rapidly progressive nature of the condition. A minimal or fat free diet may be used to reduce accumulation of LAL substrates (cholesteryl esters and triglycerides) in the body (also called dietary substrate reduction). [8] Intravenous nutritional support is also provided. [1] Medication may be needed to supplement adrenal hormones as adrenal gland dysfunction is common. Hematopoietic stem cell transplant may be used in some people. [8] _x000D_ _x000D_ The NICE evaluation of sebelipase alfa for treating LAL deficiency (ID737) has been paused while this evaluation for treating Wolman disease is undertaken._x000D_ _x000D_ References_x000D_ 1. National Organization for Rare Disorders. (2021) Wolman disease. Accessed September 2021._x000D_ 2. Orphanet. (2021) Wolman disease. Accessed September 2021._x000D_ 3. Jones SA, Valayannopoulos V, Schneider E et al. (2016) Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med 18(5):452–458._x000D_ 4. National Organization for Rare Disorders. (2021) Cholesteryl ester storage disease. Accessed September 2021._x000D_ 5. Aguisanda F, Thorne N, Zheng W. (2017) Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development. Curr Chem Genom Transl Med 11:1–18._x000D_ 6. Online Mendelian Inheritance in Man (OMIM). (2021) Lysosomal acid lipase deficiency. Accessed September 2021._x000D_ 7. NHS England. (2021) NHS England drugs list v16.1, 2021-2022. Accessed November 2021._x000D_ 8. Potter JE, Petts G, Ghosh A et al. (2021) Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease. Orphanet J Rare Dis 16:235.

Lay abstract: To evaluate the benefits and costs of sebelipase alfa for treating Wolman disease for national commissioning by NHS England.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: METABOLIC AND ENDOCRINE