Title: Cipaglucosidase alfa with miglustat for treating Pompe disease [ID3771]
Funder: Department of Health and Social Care

Abstract: Pompe disease, also known as glycogen storage disease type II or acid maltase deficiency is a rare inherited genetic disorder caused by the mutation of the GAA gene which makes an enzyme called acid alpha-glucosidase, resulting in the deficiency of this enzyme. [1] This leads to the progressive accumulation of glycogen, a sugar usually stored in multiple tissues including around the heart, skeletal muscles, respiratory muscles, vascular, gastrointestinal and nervous systems. [1],[2] The signs and symptoms of Pompe disease are directly related to the muscles affected. The respiratory, skeletal and cardiac muscles are most profoundly affected. Other symptoms include pain, mental fatigue and an impact on mental health. _x000D_ _x000D_ Pompe disease is classified in two subtypes. The infantile onset and the late onset. The late onset usually presents from 1 year of age and is characterised by a progressive myopathy (with little or no cardiac involvement) which can lead to severe morbidity, respiratory failure and early mortality. [3],[4] While acid alpha-glucosidase activity is typically absent or nearly absent in infantile onset Pompe disease, there is still some residual activity present in those with late onset Pompe disease.[5] _x000D_ _x000D_ In 2019 in the EU, Pompe disease was estimated to affect approximately 0.3 in 10,000 people. [6] In 2018 in the EU, the reported birth prevalence was 0.8 per 100,000 people for the infantile onset form and 1.75 per 100,000 for the late-onset form according to European Orphanet data. [7] _x000D_ _x000D_ Current clinical management includes enzyme replacement therapy (ERT) with alglucosidase alfa which aims to replace the missing or malfunctioning enzyme. The decision to start treatment is usually based on a set of criteria including confirmed diagnosis and the patient should be symptomatic, have residual skeletal and respiratory muscle function and not have another advanced stage life-threatening condition. [8] Supportive treatment is also needed and can include physiotherapist, occupational therapist, speech therapist and dietetician. [3]_x000D_ _x000D_ References_x000D_ 1. Xu S, Lun Y, Frascella M, Garcia A, Soska R, Nair A, et al. Improved efficacy of a next-generation ERT in murine Pompe disease. JCI Insight. 2019 Mar 7;4(5)._x000D_ Available from: https://www.ncbi.nlm.nih.gov/pubmed/30843882 10.1172/jci.insight.125358_x000D_ 2. Lim JA, Sun B, Puertollano R, Raben N. Therapeutic Benefit of Autophagy Modulation in Pompe Disease. Mol Ther. 2018 Jul 5;26(7):1783-96. _x000D_ Available from: https://www.ncbi.nlm.nih.gov/pubmed/29804932_x000D_ 3. National Health Service - Cambridge University Hospitals. Pompe._x000D_ Available from: https://www.cuh.nhs.uk/addenbrookeshospital/services/lysosomal-disorders/disorders/pompe Accessed August 2022_x000D_ 4. Van der Ploeg AT, Reuser AJ. Pompe's disease. Lancet. 2008 Oct 11;372(9646):1342-53. _x000D_ Available from: https://www.ncbi.nlm.nih.gov/pubmed/18929906_x000D_ 5. Chan J, Desai AK, Kazi ZB, Corey K, Austin S, Hobson-Webb LD, et al. The emerging phenotype of late-onset Pompe disease: A systematic literature review. Molecular genetics and metabolism. 2017 Mar 1;120(3):163-72. Available from: https://www.sciencedirect.com/science/article/pii/S1096719216302967_x000D_ 6. European Medicines Agency (EMA). Miglustat for the treatment of glycogen storage disease type II (Pompe's disease). _x000D_ Available from: https://www.ema.europa.eu/en/documents/orphandesignation/eu/3/18/2129-public-summary-opinion-orphan-designationmiglustat-treatment-glycogen-storage-disease-type-ii_en.pdf_x000D_ 7. Orphanet – Prevalence and incidence of rare diseases: Bibliographic data. Available from https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_diseases.pdf Accessed August 2022_x000D_ 8. Van der Ploeg AT, Kruijshaar ME, Toscano A, Laforet P, Angelini C, Lachmann RH, et al. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease: a 10-year experience. Eur J Neurol. 2017 Jun;24(6):768-e31. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28477382

Lay abstract: To appraise the clinical and cost effectiveness of cipaglucosidase alfa with miglustat within its marketing authorisation for treating Pompe disease.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CONGENITAL DISORDERS