The longest-running bet in anticoagulation — that you can blunt clotting without provoking dangerous bleeds — just drew one of its largest tests. Regeneron has registered ROXI-EVEREST, a Phase 3 trial designed to enroll a planned 15,364 adults with atrial fibrillation, comparing its investigational Factor XI antibody against the standard-of-care anticoagulant apixaban. The study is listed as not yet recruiting, with an estimated start of July 31, 2026.
The drug, cenvacibart (REGN7508), is a monoclonal antibody targeting Factor XI, a clotting factor that several companies are pursuing on the theory that inhibiting it prevents pathological clots while sparing the normal hemostasis whose disruption drives anticoagulant bleeding. ROXI-EVEREST will randomize patients with paroxysmal or persistent AF and elevated stroke risk — broadly, a CHA2DS2-VA score of 2 or higher — in a quadruple-blind, double-dummy design, in which each arm receives an active drug plus a matching placebo for the other.
Two primary endpoints, one trade-off
The trial is built around the central tension of the class. Its co-primary endpoints are time to first stroke or systemic embolism — the efficacy question — and time to first ISTH major or clinically relevant non-major bleeding — the safety question. Both are measured over roughly 36 months.
The design forces the drug to answer both questions at once: prevent strokes as well as apixaban, and bleed less.
Secondary endpoints stack composite efficacy-plus-bleeding outcomes, all-cause death, hemorrhagic stroke, and anti-drug antibody formation — a relevant concern for an injectable biologic in a chronic indication.
No efficacy or safety data exist yet; this is a registration, not a result. Estimated primary completion is September 11, 2029. Whether a Factor XI antibody can unseat the direct oral anticoagulants now depends on what those 15,364 patients eventually show.