Only investigational RNAi therapy in development for all three known types of PH
We are developing nedosiran, the only RNAi drug candidate in development for primary hyperoxaluria (PH) types 1, 2 and 3. Nedosiran is Dicerna’s most advanced product candidate utilizing our proprietary GalXC™ RNAi technology. PH is a family of ultra-rare, life-threatening genetic disorders that initially manifest with complications in the kidneys. Nedosiran is designed to inhibit production of the hepatic lactate dehydrogenase (LDH) enzyme – an enzyme that catalyzes the final step in the glyoxylate metabolism pathway that can lead to oxalate overproduction in patients with PH1, PH2 or PH3. Dicerna is evaluating the safety and efficacy of nedosiran in patients with all known types of PH as part of its PHYOX™ clinical development program.
Preventing excess oxalate production
There are three known types of PH (PH1, PH2 and PH3), each resulting from a mutation in one of three different genes in the glyoxylate metabolism pathway: AGXT, GRHPR and HOGA1 respectively. Abnormal production and accumulation of oxalate leads to recurrent kidney stones, nephrocalcinosis and chronic kidney disease that may progress to end-stage kidney disease requiring intensive dialysis and systemic deposition of oxalate in various tissues in the body including the retina, bones, cardiac muscle and elsewhere. Nedosiran is designed to inhibit the production of hepatic lactate dehydrogenase (LDH) enzyme in the final common step of this pathway with the goal of preventing this overproduction of oxalate. This LDH enzyme inhibition occurs specifically in the liver due to the incorporation of GalNAc-targeting ligands in nedosiran that bind specifically to the asialoglycoprotein receptors (ASGPR) on hepatic cell surfaces.