Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx: Results of Phase 1 and Phase 2 Studies.
Targeting angiotensinogen (AGT) may provide a novel approach to more optimally inhibit the renin-angiotensin-aldosterone system pathway. Double-blind, placebo-controlled clinical trials were performed in subjects with hypertension as monotherapy or as an add-on to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with IONIS-AGT-LRx versus placebo up to 2 months. IONIS-AGT-LRx was well tolerated with no significant changes in platelet count, potassium levels, or liver and renal function. IONIS-AGT-LRx significantly reduced AGT levels compared with placebo in all 3 studies. Although not powered for this endpoint, trends were noted in blood pressure reduction. In conclusion, IONIS-AGT-LRx significantly reduces AGT with a favorable safety, tolerability, and on-target profile. (A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx; NCT04083222; A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Subjects With Controlled Blood Pressure; NCT03714776; Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ionis AGT-LRx in Healthy Volunteers; NCT03101878).
['Morgan|Erin S|ES|', 'Tami|Yvonne|Y|', 'Hu|Kuolung|K|', 'Brambatti|Michela|M|', 'Mullick|Adam E|AE|', 'Geary|Richard S|RS|', 'Bakris|George L|GL|', 'Tsimikas|Sotirios|S|']
antisense angiotensinogen hypertension ACEi/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker AGT, angiotensinogen ASO, antisense oligonucleotide CI, confidence interval DBP, diastolic blood pressure EDTA, ethylenediaminetetraacetic acid GalNAc3, triantennary N-acetyl galactosamine K+, potassium PS, phosphorothioate RAAS RAAS, renin-angiotensin-aldosterone system SBP, systolic blood pressure hepatocyte oligonucleotide