Positive results have been reported from a trial of siRNA—small interfering RNA—therapy targeting coagulation factor XI (FXI) in patients with chronic coronary artery disease.
The randomised, double-blind, placebo-controlled European Phase 2a study assessing vortosiran (Ribocure Pharmaceuticals) involved patients with chronic coronary artery disease with previous myocardial infarction (MI) receiving aspirin.
Presenting the results at the China Pharmaceutical Innovation Conference (CPIC; 22–24 July, Shanghai, China), investigators reported that the agent was generally well tolerated and achieved profound, dose-dependent, and long-lasting suppression of factor XI activity, Ribocure Pharmaceuticals states in a press release.
Patients completing the high dose group vortosiran dosing regimen, at a maintenance dose of 400mg, achieved a mean maximum reduction in FXI activity of 92%, which was sustained for several months following dosing.
No treatment-related serious adverse events, major bleeding events, or clinically relevant non-major bleeding events were observed.
The findings provide the first clinical proof-of-concept for siRNA-mediated factor XI suppression in patients with coronary artery disease, supporting the potential of vortosiran as a differentiated, long-acting antithrombotic therapy, the company press release adds.
By targeting FXI, vortosiran aims to reduce thrombotic risk while preserving haemostasis, potentially addressing a major unmet need in cardiovascular disease.
“Preventing blood clots without increasing bleeding risk has long been a holy grail of cardiovascular medicine. These phase 2a data, generated in the target patient population on top of standard of care, reinforce our belief that vortosiran is a safe and highly differentiated FXI-inhibition approach for thromboembolic diseases. Building on these findings, we have initiated the ORBIT-XI programme, including several phase 2b trials designed to support rapid progression into phase 3 development across multiple indications,” comments Li-Ming Gan, co-CEO and global president of research & development, Ribocure Pharmaceuticals.
