IONIS-AGT-LRx significantly reduced plasma angiotensinogen levels compared to placebo in patients with controlled hypertension after washout (-54%) and in patients with uncontrolled hypertension on 2 to 3 medications (-67%).
RCT (n=51)
Double-blind
2:1
Yes
Does IONIS-AGT-LRx reduce angiotensinogen levels and blood pressure in subjects with hypertension?
IONIS-AGT-LRx safely and effectively reduces angiotensinogen levels in hypertensive patients, representing a novel approach to RAAS inhibition.
Absolute Event Rate: -67% vs 3.4%
p-value: p=<0.001
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 et al. (Mon,) conducted a rct in Hypertension (n=51). IONIS-AGT-LRx vs. Placebo was evaluated on Percent change from baseline to study week 9 in plasma angiotensinogen (Add-on study) (p=<0.001). IONIS-AGT-LRx significantly reduced plasma angiotensinogen levels compared to placebo in patients with controlled hypertension after washout (-54%) and in patients with uncontrolled hypertension on 2 to 3 medications (-67%).