Title: Vutrisiran for treating hereditary transthyretin-related amyloidosis [ID5074]
Funder: Department of Health and Social Care

Abstract: Hereditary transthyretin-related amyloidosis (hATTR) affects people born with inherited mutations in the transthyretin gene. This causes the liver to produce abnormal transthyretin protein which accumulates as deposits in the tissues of the body (amyloidosis). These accumulated deposits can disrupt the structure and damage the function of the affected tissues. Most commonly deposits accumulate in the peripheral nervous system or in the tissues of the heart. Over time, these deposits can cause symptoms of polyneuropathy (such as pain, loss of sensation and weakness in the hands, arms, legs or feet) and symptoms of cardiomyopathy (such as chest pain, shortness of breath and fluid overload). In some cases, the autonomic nervous system which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by amyloidosis. _x000D_ _x000D_ The condition is progressive and the neuropathy can be classified into 4 stages. Stage 0 denotes asymptomatic disease, people with stage I disease have mild symptoms and can walk, people with stage II disease have moderate symptoms and require assistance to walk, and people with stage III disease have severe symptoms and need to use a wheelchair or are bedbound. The effects and complications of the disease can lead to death within 5 to 15 years of symptoms developing. _x000D_ _x000D_ The prevalence of hATTR amyloidosis is estimated to be less than 1 in 100,000 people in the general European population.1 In the UK there are thought to be around 150 people with the disease._x000D_ _x000D_ Current treatment options for people with hATTR amyloidosis include symptom relief and supportive care including pain management, nutritional and mobility support and mitigation of the effects of the disease on other organs. Patisirian is recommended for treating hATTR amyloidosis in adults with stage 1 and stage 2 polyneuropathy (HST10). Inotersen is recommended for treating stage 1 and stage 2 polyneuropathy in adults with hATTR amyloidosis (HST 9). Diflunisal is a non-steroidal anti-inflammatory drug which makes transthyretin less likely to form amyloid accumulations. It is sometimes used outside of its marketing authorisation to treat hATTR amyloidosis. It is contraindicated in people with cardiac impairment and those taking anticoagulants. _x000D_ _x000D_ Liver transplantation, which prevents the formation of additional amyloid deposits by removing the main source of abnormal transthyretin production, is an option for some people with a specific genetic mutation. However, this mutation is uncommon in England, and transplantation can only take place early in the course of the disease, so it is very rarely used in England. _x000D_ _x000D_ References_x000D_ 1. Orpha.net. Prevalence of rare diseases. Bibliographic data (June 2022). https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf

Lay abstract: To appraise the clinical and cost effectiveness of vutrisiran within its marketing authorisation for treating hereditary transthyretin-related amyloidosis.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CONGENITAL DISORDERS