Title: Lumasiran for treating primary hyperoxaluria type 1 [ID3765]
Funder: Department of Health and Social Care

Abstract: Primary hyperoxaluria type 1 is a genetic disorder caused by mutations of the AGXT gene, which causes excess oxalate production leading to oxalate crystals building up in the kidneys and urinary tract. Signs and symptoms of primary hyperoxaluria type 1 vary in severity and may begin any time from infancy to early adulthood. Children with primary hyperoxaluria type 1 who have symptoms during infancy generally have the most severe disease course, characterised by rapid progression to renal failure. Symptoms may include recurrent kidney stones; blood in the urine; and urinary tract infections. Left untreated, primary hyperoxaluria type 1 can result in end-stage renal disease accompanied by systemic oxalate deposition in the eyes, skin and bone marrow, which is life-threatening. [1] It is estimated that about a third of people with primary hyperoxaluria type 1 have end-stage renal disease at diagnosis and only a quarter of people will retain kidney function 30 years after diagnosis. [2]_x000D_ _x000D_ Around 120 people in the UK have hyperoxaluria as of October 2021, according to the National Registry of Rare Kidney Diseases (RaDaR). [3] Approximately three quarters of people with primary hyperoxaluria are diagnosed as type 1.[4] The median age at diagnosis is around 7 to 10 years in people with primary hyperoxaluria. [5] The incidence of primary hyperoxaluria type 1 in Europe has been estimated as 1 in 100,000 live births per year.[6] _x000D_ _x000D_ The aim of treatment for people with primary hyperoxaluria type 1 is to reduce oxalate levels, therefore preventing complications associated with hyperoxaluria, such as the formation of kidney stones or worsening kidney function. This can be done by taking vitamin B6, which may reduce oxalate levels in some people. [7] Several dietary measures can also be taken to try and prevent kidney stones forming, for example drinking lots of fluids and avoiding foods with high levels of oxalate. In clinical practice, for infants with rapidly progressing disease, haemodialysis and hyperhydration are used to try to stop progression. Depending on the response to other treatments and the disease severity, options include; a combined liver kidney transplant or a sequential liver kidney transplant or an isolated liver transplant.[8]_x000D_ _x000D_ References_x000D_ 1. Genetic and Rare Diseases Information Center. Primary hyperoxaluria type 1. Available from: https://rarediseases.info.nih.gov/diseases/2835/primaryhyperoxaluria-type-1. Accessed November 2021._x000D_ 2. Zhao F, Bergstralh EJ, Mehta RA, et al. Predictors of incident ESRD among patients with primary hyperoxaluria presenting prior to kidney failure. Clinical Journal of American Society of Nephrology. 2016, 11 (1), 119–1263._x000D_ 3. National Registry of Rare Kidney Diseases (RaDaR). 2021. Available from: https://ukkidney.org/rare-renal/metadata. Accessed November 2021._x000D_ 4. Lieske JC, Monico CG, Holmes WS, et al. International Registry for Primary Hyperoxaluria. American Journal of Nephrology. 2005, 25, 290–296._x000D_ 5. Ben-Shalom E, Frishberg Y. Primary hyperoxalurias: diagnosis and treatment. Pediatric Nephrology. 2015, 30, 1781–1791._x000D_ 6. Harambat J, Fargue S, Bacchetta J, et al. Primary Hyperoxaluria. International Journal of Nephrology. 2011, ID 864580._x000D_ 7. Hoyer-Kuhn H, Kohbrok S, Volland R, et al. Vitamin B6 in Primary Hyperoxaluria I: First Prospective Trial after 40 Years of Practice. Clinical Journal of American Society of Nephrology. 2014, 9 (3), 468–477._x000D_ 8. Milliner DS, Harris PC, Cogal AG, et al. Primary Hyperoxaluria Type 1. GeneReviews. Updated November 30, 2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1283/ Accessed November 2021.

Lay abstract: To appraise the clinical and cost effectiveness of lumasiran within its marketing authorisation for treating primary hyperoxaluria type 1.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL