Ionis Pharmaceuticals has announced positive results from a phase 2b study of fesomersen, an investigational antisense medicine designed to reduce the production of Factor XI for the prevention of thrombosis, in patients with end-stage renal disease (ESRD) on haemodialysis.
The RE-THINC ESRD study was conducted by Bayer, which partnered with Ionis in 2015 to develop the drug. However, the companies have now terminated the agreement, with the rights and licences granted to Bayer under the collaboration being returned to Ionis.
The trial met its primary endpoint, demonstrating no increase in the incidence of the composite of major bleeding and clinically relevant non-major bleeding with 24 weeks of treatment.
The study also demonstrated dose-dependent and sustained median reductions in steady-state Factor XI levels of 53.1%, 72.2% and 86.6% in the 40mg, 80mg, and 120mg doses of fesomersen, respectively, administered once every four weeks.
Incidences of dialysis circuit clotting and arteriovenous access thrombosis also diminished significantly with decreasing Factor XI levels, the company reported, both of which were exploratory efficacy endpoints.
Thrombosis occurs when blood clots block the blood vessels, which can obstruct blood flow and prevent sufficient oxygen flow to tissues and organs.
Current anti-thrombotic treatments include anticoagulants such as warfarin, Factor Xa inhibitors and thrombin inhibitors. Despite these therapies proving effective at lowering the risk of thrombosis, they can place patients at a significant risk of bleeding because they target factors required for normal coagulation, Ionis reported.
Fesomersen is an investigational antisense medicine designed by Ionis to reduce the production of Factor XI, a clotting factor produced in the liver that, in high levels, can increase the risk of thrombosis.
Alternatively, individuals deficient in Factor XI have a lower incidence of thrombosis-related events and little to no increase in bleeding risk, making Factor XI an attractive target for an anti-thrombotic medicine.
Commenting on the positive results, Richard Geary, executive vice president and chief development officer at Ionis, said: “We are very pleased with the efficacy and safety data seen in the phase 2b study of fesomersen in patients with ESRD, which we believe supports continued advancement of this potential novel anti-thrombotic therapy for patients with renal and cardiovascular diseases.
“We thank Bayer for their partnership in the development of fesomersen. We are focused on getting fesomersen into the hands of a new partner to deliver it to the market and patients in need.”