Title: Lanadelumab for preventing recurrent attacks of hereditary angioedema [ID1268]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of lanadelumab within its marketing authorisation for preventing recurrent attacks of hereditary angioedema.

Lay abstract: Hereditary angioedema (HAE) is an rare genetic disorder, associated with the deficiency of the protein C1-esterase inhibitor, which is a regulator of inflammatory pathways. Normally, C1-esterase inhibitor controls the enzyme cascade reactions so that uncontrolled swelling of the subcutaneous and submucosal tissues do not occur. In patients with HAE, at times of physiological or psychological stress, the function of the C1-esterase inhibitor is insufficient, resulting in the accumulation of excessive fluid (oedema) and localised oedematous swellings. The swellings usually occur in the mouth, the gut (affecting the submucosal tissues) and the airway, causing difficulty with breathing (with potential asphyxia) and severe pain in the stomach. The swellings can also occur in the deep tissues of the skin (affecting the dermis and subcutaneous tissues) causing significant impact for example if the hands, feet or genitals are affected. Most angioedema attacks are associated with trauma, medical procedures, emotional stress, menstruation, oral contraceptive use, infections, or the use of medications such as ACE inhibitors. Attacks are unpredictable; severity and frequency of previous attacks do not predict severity and frequency of future attacks. Attacks usually last approximately 2 to 5 days before resolving spontaneously. There are 2 types of HAE where the deficiency of the protein C1-esterase inhibitor occurs. These account for almost all cases of HAE (1): • type I is defined by low levels of a normal protein C1-esterase inhibitor in the plasma. • type II is defined by normal level of a dysfunctional protein C1-esterase inhibitor in the plasma. It is estimated that HAE affects between 1 per 50,000 to 1 per 100,000 of the population.(1) Most cases develop in childhood and some cases develop in early adulthood. HAE usually occurs during the first 10 to 20 years of life. There are broadly 3 approaches to managing HAE: avoidance of precipitating factors (e.g. minor trauma, hormone replacement therapy), acute treatments and preventive (prophylactic) treatments of acute attacks. Short-term preventive treatments aim to prevent an attack before known triggers which include, for example, dental work or surgery, whereas long-term preventative treatments are used routinely to reduce the need for treatment of acute attacks. As a long-term strategy, attenuated androgens (such as danazol) or C1-esterase inhibitor (such as Cinryze) can be used. Danazol does not have a marketing authorisation in the UK for HEA. Anti-fibrinolytics, such as tranexamic acid, can also be used. References 1 NHS Clinical commissioning: plasma derived C1-esterase inhibitor for prophylactic treatment of HAE (2013). Accessed May 2018 https://www.england.nhs.uk/commissioning/wp- content/uploads/sites/12/2013/05/16045_FINAL.pdf

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CONGENITAL DISORDERS