Lumasiran is in clinical development for the treatment of primary hyperoxaluria type I (PH1). PH1 is a very rare disease caused by certain genetic mutations, in which excess oxalate production results in the deposition of oxalate crystals in the kidneys and urinary tract. This leads to stone formation and kidney failure with significant morbidity and mortality. Treatment options for PH1 include vitamin B6 which is known to reduce the body’s production of oxalate, dietary recommendations to prevent kidney stones and combined liver-kidney transplantation before or after development of end-stage kidney failure.
Lumasiran, which is administered as a subcutaneous injection, is designed to reduce the levels of an enzyme called glycolate oxidase produced by the liver. Oxalate production is therefore inhibited. By reducing oxalate production, lumasiran has the potential to prevent the actual disease process that develops in PH1. If licensed, lumasiran may provide the first pharmacological treatment option for patients with PH1 who do not have any approved treatment.
Fedovapagon works directly in the collecting ducts of the kidney by binding to, and activating receptors that causes the kidneys to reabsorb water from urine as it passes towards the bladder. If fedovapagon is administered before going to bed the result is less urine produced overnight. Therefore, if licensed, fedovapagon would be the first medicinal product specifically for the treatment of nocturia in men with enlarged prostates.