Lumasiran for Primary Hyperoxaluria Type 1

Primary hyperoxalurias are a group of rare genetic diseases. There are 3 subtypes each resulting in the overproduction of oxalate by the liver. Type 1 is the most common type, which accounts for approximately 80% of cases and occurs as a result of a genetic defect in the alanine:glyoxylate aminotransferase (AGXT) gene that encodes the enzyme alanine glyoxylate aminotransferase. Defect in the enzyme results in overproduction of oxalate, which leads to deposition of calcium oxalate crystals in the kidneys and urinary tract. The result is the formation of painful and recurrent nephrolithiasis (renal stones), nephrocalcinosis, and renal failure. Compromised renal function exacerbates the disease as the excess oxalate can no longer be effectively excreted, resulting in subsequent accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Lumasiran is a subcutaneously administered RNA interference (RNAi) therapeutic that silences the HAO1 gene, which encodes for a glycolate oxidase enzyme. By silencing the HAO1 gene, levels of glycolate oxidase are depleted, decreasing production of oxalate, the metabolite that directly contributes to the pathophysiology of primary hyperoxaluria type 1.