NEW YORK (GenomeWeb) – Alnylam Pharmaceuticals this month announced that it has expanded its pipeline to include ALN-AGT, a subcutaneously administered treatment for preeclampsia and other pregnancy-associated hypertensive disorders.
The drug is designed to silence angiotensinogen, the protein precursor for a peptide hormone called angiotensin II that promotes vasoconstriction as part of the renin-angiotensin system. It is delivered subcutaneously using Alnylam's GalNAc conjugates.
According to Alnylam, gain-of-function human mutations or variants of AGT are associated with increased risk of hypertension — a hallmark of preeclampsia — in pregnant women. However, small-molecule inhibitors of the renin-angiotensin system cross the placental barrier and are associated with fetal toxicity, preventing their therapeutic use.
Earlier this year, the company and academic collaborators presented rodent data in a preeclampsia model showing that ALN-AGT could knock down maternal AGT in the liver without affecting the fetus, significantly improve pregnancy-related hypertension, ameliorate preeclamptic sequelae such as proteinuria in the mother, and improve fetal outcomes.