Ichorcumab (JNJ-64179375) / J&J - LARVOL DELTA

EMERGING ANTICOAGULANTS FOR THE THROMBOPROPHYLAXIS OF ATRIAL FIBRILLATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE. (WSMRF 2022) - "Summary of Results The four anticoagulants we found matching our inclusion criteria includes Betrixaban, Fondaparinux, Tecafarin and Ichorcumab. Tecarfarin has most of the benefits associated with warfarin but with less drug-drug interaction and a decrease kidney dependent metabolism...Conclusions Our review suggests there are multiple novel anticoagulants that may diversify the current EHRA and AHA recommendations for patients with concomitant Afib and ESRD. Although these therapies have demonstrated non-inferiority to warfarin, higher level trials are needed to further establish their therapeutic index and efficacy in the context of Afib and ESRD."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Nephrology • Pediatrics • Renal Disease

Translational PK/PD and model-informed development of JNJ-67842125, a F reversal agent for JNJ-64179375, a long-acting thrombin inhibitor. (PubMed, Br J Pharmacol) - "The results enabled selection of JNJ-67842125 as the RA for JNJ-9375."

Journal • PK/PD data

Randomized Phase 2 Trial Comparing JNJ-9375, a Thrombin-directed Antibody, with Apixaban for Prevention of Venous Thrombosis. (PubMed, J Thromb Haemost) - "JNJ-9375 was safe but less effective than apixaban. This may reflect weak thrombin inhibition or inability of JNJ-9375 to attenuate the growth of thrombi that formed before drug administration."

Clinical • Journal • P2 data • Cardiovascular • Hematological Disorders • Orthopedics • Thrombosis • Venous Thromboembolism

Pharmacological Profile of JNJ-64179375: A Novel, Long Acting Exosite-1 Thrombin Inhibitor. (PubMed, J Pharmacol Exp Ther) - "Bleeding was increased at 3 mg/kg in a rat tail transection bleeding model demonstrating a therapeutic index of 10× compared with 1× for apixaban in the same models. In an in vivo rat AV shunt model, JNJ-9375 prevented thrombus formation in a dose dependent fashion while demonstrated reduced bleeding risk. The present study demonstrated the anti-thrombotic effects of inhibiting the exosite I region of thrombin when given in a prevention mode in preclinical animal models."

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Thrombin Exosite 1 Inhibition with JNJ-64179375 Inhibits Thrombus Formation in a Human Translational Model of Thrombosis. (PubMed, Cardiovasc Res) - "In preclinical studies, JNJ-9375 demonstrated robust antithrombotic protection with a wider therapeutic index when compared to apixaban...Fifteen healthy volunteers participated in a double-blind randomized crossover study of JNJ-9375 (2.5, 25, and 250 μg/mL), bivalirudin (6 μg/mL; positive control), and matched placebo...Exosite 1 inhibition with JNJ-9375 caused prolongation of blood coagulation, selective inhibition of thrombin-mediated platelet activation, and reductions in ex vivo thrombosis driven by a decrease in fibrin-rich thrombus formation. JNJ-9375 represents a novel class of anticoagulant with potential therapeutic applications."

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