China-based Hengrui Pharmaceuticals has announced positive top-line results from a Phase III confirmatory study evaluating SHR-2004, a first-in-class humanised monoclonal antibody (mAb) targeting coagulation Factor XI (FXI) and activated FXIa, for venous thromboembolism (VTE) prophylaxis after total knee arthroplasty (TKA).

Conducted across 111 centres with 1,165 patients, the randomised, double-blind trial compared intravenous (90 mg) and subcutaneous (120 mg) single-dose SHR-2004 administered 4–8 hours post-operation versus daily subcutaneous enoxaparin (40 mg). At day 12, VTE rates were 10.6%, 16.1%, and 21.9% respectively, with the intravenous arm meeting the prespecified superiority endpoint (p<0.0001). Consistent benefit was observed across all subgroups, with composite bleeding rates of 1.9% and 2.1% versus 1.9% for enoxaparin, demonstrating a favourable safety profile without new signals.

SHR-2004 is designed to block the intrinsic thrombotic amplification pathway while preserving haemostatic function, addressing limitations of low-molecular-weight heparins (daily injections, thrombocytopoenia risk) and direct oral anticoagulants (early postoperative dosing challenges, renal constraints, bleeding risk). As the first FXI antibody to achieve positive Phase III results in orthopaedic VTE prevention, Hengrui plans to submit a New Drug Application (NDA) in China in 2026, positioning the asset as a differentiated, convenient alternative in the prophylactic anticoagulation market.