Positive Phase 2A Results for Vortosiran in Chronic Coronary Disease Announced

RIBOLIFE-B (ASX: 06938) has announced the presentation of positive results from a European Phase 2a study evaluating vortosiran (RBD4059) in patients with chronic coronary artery disease (CAD). The data was shared at the Global Conference on Innovative Therapeutics held in Shanghai.

The randomized, double-blind, placebo-controlled trial assessed vortosiran, a small interfering RNA (siRNA) therapy targeting coagulation factor XI (FXI). In chronic CAD patients with a history of myocardial infarction who were also receiving standard aspirin therapy, vortosiran demonstrated a favorable overall tolerability profile.

The therapy achieved a significant, dose-dependent, and durable suppression of FXI activity. Patients who completed the high-dose regimen, maintained at 400 mg, experienced an average maximum reduction in FXI activity of 92%. This effect persisted for several months post-administration.

These findings support the potential for a dosing interval of every three to six months across different indications. The level of FXI inhibition observed is notably higher than the estimated levels for small molecule drugs in Phase 3 development, which typically require once- or twice-daily dosing.

A key outcome of the trial was the absence of any treatment-related serious adverse events, major bleeding events, or clinically relevant non-major bleeding events.

This study provides the world's first clinical proof-of-concept for siRNA-mediated FXI inhibition in CAD patients. The results underscore vortosiran's potential as a differentiated, long-acting antithrombotic therapy.

By specifically targeting FXI, vortosiran is designed to reduce the risk of thrombosis while preserving the body's natural hemostatic function. This approach aims to address a significant unmet medical need in the field of cardiovascular disease.

Vortosiran is a GalNAc-conjugated siRNA drug candidate developed internally using the RiboGalSTARTM liver-targeting technology platform. It works by specifically inhibiting the synthesis of FXI, thereby blocking the intrinsic coagulation pathway to achieve potent antithrombotic activity.

Strong human genetic evidence indicates that individuals with naturally lower FXI levels have a reduced probability of thrombotic events without a corresponding increase in spontaneous bleeding risk. Consequently, FXI inhibition has emerged as a highly promising therapeutic strategy, offering effective thrombosis prevention with a potentially superior safety profile compared to existing anticoagulant therapies.