Ribo’s siRNA therapy vortosiran achieved 92% Factor XI suppression with no major bleeding in a Phase 2a trial in chronic coronary artery disease, supporting Phase 2b and Phase 3 development.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Suzhou Ribo Life Science and its subsidiary Ribocure Pharmaceuticals AB have reported positive Phase 2a results for vortosiran (RBD4059), an investigational small interfering RNA (siRNA) therapy targeting coagulation Factor XI (FXI), in patients with chronic coronary artery disease (CAD). The findings were presented at the China Pharmaceutical Innovation Conference (CPIC) in Shanghai.
The randomized, double-blind, placebo-controlled European study (NCT06717074) evaluated vortosiran in patients with chronic CAD who had a previous myocardial infarction and were receiving standard-of-care aspirin therapy. The treatment was generally well tolerated and produced profound, dose-dependent, and long-lasting suppression of FXI activity, supporting infrequent dosing every three to six months.
Long-Acting FXI Inhibition for Thrombosis Prevention
Vortosiran is a GalNAc-conjugated siRNA developed using Ribo’s proprietary RiboGalSTAR™ liver-targeting platform. The therapy suppresses hepatic production of Factor XI, a key component of the intrinsic coagulation pathway involved in thrombus formation.
Factor XI has become an attractive therapeutic target because genetic studies have shown that people with naturally lower FXI levels experience fewer thrombotic events without a corresponding increase in spontaneous bleeding. This has raised interest in developing anticoagulants that reduce clotting while preserving normal hemostasis, potentially overcoming one of the major limitations of current blood-thinning therapies.
Phase 2a Trial Demonstrated Durable FXI Suppression
The Phase 2a trial enrolled patients with chronic coronary artery disease and a history of myocardial infarction who remained on aspirin therapy.
Patients receiving the highest maintenance dose of vortosiran (400 mg) achieved a mean maximum reduction of 92% in Factor XI activity. The suppression persisted for several months after dosing, suggesting that administration every three to six months may be sufficient across multiple cardiovascular indications.
According to the company, the magnitude of FXI inhibition exceeded levels reported for oral small-molecule FXI inhibitors in Phase 3 trials.
Investigators reported no treatment-related serious adverse events, no major bleeding events, and no clinically relevant non-major bleeding events during the study.
The findings provide the first clinical proof-of-concept demonstrating that siRNA-mediated suppression of Factor XI can achieve sustained anticoagulant activity in patients with coronary artery disease while maintaining a favorable safety profile.
Company Highlights Clinical Potential
Dr. Li-Ming Gan, Co-Chief Executive Officer and Global President of Research and Development at Ribo, said preventing thrombosis without increasing bleeding risk remains one of the greatest challenges in cardiovascular medicine.
He noted that the study validates vortosiran as a differentiated, long-acting FXI inhibition strategy in patients receiving standard cardiovascular care and supports continued development across thromboembolic diseases.
ORBIT-XI Program Advances Toward Late-Stage Development
Building on the Phase 2a findings, Ribo has initiated the ORBIT-XI (Optimizing RNA-Based Inhibition of Thrombosis) clinical program. The program includes several Phase 2b studies intended to support rapid advancement into Phase 3 development across multiple thromboembolic indications.
If future studies confirm these efficacy and safety findings, vortosiran could offer a long-acting anticoagulant option requiring only two to four doses per year, potentially improving treatment adherence while maintaining protection against thrombotic events without increasing clinically significant bleeding.
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About the Writer
Meghana Jinka (LinkedIn) is a Pharm.D graduate with a strong interest in clinical pharmacy, clinical research, pharmacovigilance, and medical writing. She has developed expertise in evaluating scientific literature, interpreting clinical data, and communicating complex medical information in a clear and accessible manner. Through clinical training, patient counseling, and healthcare awareness activities, she has gained practical experience in evidence-based medicine and patient-centered care. Passionate about healthcare communication, Meghana is committed to developing accurate, engaging, and evidence-based healthcare documents that support healthcare professionals and the wider community.