Antisense inhibition of angiotensinogen with IONIS-AGT-LRx: Results of Phase 1 and Phase 2 studies

Summary Targeting angiotensinogen may provide a novel approach to more optimally inhibit the RAAS pathway. Double-blind, placebo-controlled clinical trials were performed in subjects with hypertension as monotherapy or Add-On to ACEi/ARB 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 angiotensinogen levels compared to 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 angiotensinogen with a favorable safety, tolerability, and on-target profile