Ionis Pharmaceuticals, Inc. announced positive topline results of the Phase 2b RE-THINC ESRD study of fesomersen, formerly IONIS-FXI-LRx, in patients with end-stage renal disease (ESRD) on hemodialysis. In the study, fesomersen achieved its primary outcome measure of no increase in incidence of major bleeding and clinically relevant non-major bleeding as compared to placebo. Data from the study show that fesomersen, administered monthly at 40 mg, 80 mg and 120 mg for up to 48 weeks, was safe and well-tolerated.

Fesomersen also demonstrated substantial and statistically significant reductions in Factor XI activity levels. Data from the study are consistent with the clinical profile seen across Ionis' other LICA programs, further validating how advancements in the company's LIgand-Conjugated Antisense technology position Ionis to deliver potentially transformative treatments for a range of unmet medical needs. The RE-THINC ESRD study was conducted by Bayer, which licensed fesomersen from Ionis.

Data from the study will be presented at an upcoming medical meeting. An estimated 17.9 million people die from cardiovascular disease each year, representing 32% of all deaths worldwide.1 Of these deaths, 85% are due to heart attacks and strokes, which are often caused by blood clots that block blood vessels in the heart or brain. Fesomersen is an investigational antisense medicine designed by Ionis to reduce the production of Factor XI, a protein produced in the liver that is an important component of the coagulation pathway.

Factor XI is an attractive target for an anti-thrombotic medicine because of its potential to separate anti-thrombotic activity from bleeding risk. The RE-THINC ESRD study focused on ESRD patients because they have a significantly high risk of thromboembolic events and also a very high bleeding risk. In prior clinical studies evaluating the safety and efficacy of the non-LICA version of fesomersen, IONIS-FXIRx, dose-dependent inhibition of Factor XI activity was demonstrated, which was associated with significant reductions in clotting events and no increase in major bleeding events.

IONIS-FXIRx was the first anti-thrombotic in development to demonstrate potential to separate anti-thrombotic activity from bleeding risk.