Title: Patisiran for treating hereditary transthyretin-related amyloidosis [ID1279]
Funder: Department of Health and Social Care

Abstract: To evaluate the benefits and costs of patisiran within its marketing authorisation for treating hereditary transthyretin-related amyloidosis for national commissioning by NHS England.

Lay 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 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. The condition is progressive and the neuropathy aspect of the disease can be classified into 4 stages. Stage 0 denotes asymptomatic disease: patients with stage I disease have mild symptoms and can walk, patients with stage II disease have moderate symptoms and require assistance to walk, and patients 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. 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. Current treatment options for people with hATTR amyloidosis are limited and mainly focus on symptom relief and supportive care including pain management, nutritional and mobility support and mitigation of the effects of the disease on other organs. Tafamidis has a marketing authorisation for treating transthyretin amyloidosis in adults with stage 1 (early) symptomatic polyneuropathy, but it is not used in clinical practice in England. 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. 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. References 1. Orpha.net. Prevalence of rare diseases. Bibliographic data (June 2018) http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_ diseases_by_alphabetical_list.pdf.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CONGENITAL DISORDERS