Lumasiran: expanding the treatment options for patients with primary hyperoxaluria type 1

Abstract

ABSTRACT Introduction Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism whereby excessive endogenous oxalate production can result in kidney failure, systemic oxalosis and early death. The approval of the first therapeutic agent to alter the treatment pathway for PH1 – lumasiran, a novel RNA interference-based drug – represents a new era in the management of patients with PH1. Areas covered A description of PH1, its pathophysiology, clinical characteristics and available treatment strategies is provided, with a focus on substrate reduction therapy and the development of lumasiran for pediatric and adult patients with PH1. Expert opinion Until very recently, treatment options for patients with PH1 have been burdensome, ineffective in preventing disease progression or associated with high morbidity. Lumasiran targets hepatic glycolate oxidase, the enzyme responsible for the synthesis of the oxalate precursor, glyoxylate. Administered subcutaneously monthly initially and then quarterly, it has been found to significantly lower urinary and plasma oxalate levels, potentially reduce the development of nephrocalcinosis and halt disease progression. For the first time, patients with PH1 have a treatment that is well tolerated, effective, and administered in a way that does not adversely impact the quality of life of those affected by this devastating disease.