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Mim8 Bispecific Antibody Prophylaxis in Hemophilia A with or without Inhibitors
Journal article   Peer reviewed

Mim8 Bispecific Antibody Prophylaxis in Hemophilia A with or without Inhibitors

Maria Elisa Mancuso, Anthony K C Chan, Chandrakala Shanmukhaiah, Chuhl Joo Lyu, Joanna Zdziarska, Johnny Mahlangu, Lize F D van Vulpen, Pratima Chowdary, Renchi Yang, Steven R Lentz, …
The New England journal of medicine, Vol.394(17), pp.1696-1709
04/30/2026
DOI: 10.1056/NEJMoa2517384
PMID: 42054679

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Abstract

Mim8 (denecimig), a bispecific antibody mimicking activated factor VIII, was developed for bleeding prophylaxis in patients with hemophilia A with or without factor VIII inhibitors. In this phase 3, randomized trial, we assigned patients 12 years of age or older with hemophilia A with or without inhibitors to receive subcutaneous Mim8 once weekly or once monthly at a dose tiered according to body weight and given in a fixed injection volume (0.8 ml). Patients who had been receiving on-demand treatment before the trial were assigned in a 1:1:1 ratio to continue on-demand treatment (group 1) or receive Mim8 once weekly (group 2a) or once monthly (group 2b). Patients who had been receiving clotting factor concentrates during a run-in phase were assigned in a 1:1 ratio to receive Mim8 once weekly (group 3) or once monthly (group 4). The first primary end point was the annualized rate of treated bleeding events (those treated with a coagulation factor product) in an evaluation of Mim8 in group 2a and Mim8 in group 2b as compared with on-demand treatment in group 1. The second was the annualized rate of treated bleeding events in an intrapatient evaluation of Mim8 in group 3 and Mim8 in group 4 as compared with clotting factor concentrate prophylaxis during the run-in phase. Of the 58 patients in the pretrial on-demand treatment cohort, 17 were assigned to group 1, 21 to group 2a, and 20 to group 2b. The estimated mean annualized rate of treated bleeding events was 0.57 (95% confidence interval [CI], 0.25 to 1.30) in group 2a and 0.20 (95% CI, 0.06 to 0.71) in group 2b, as compared with 15.76 (95% CI, 10.70 to 23.20) in group 1 (relative decrease, 96.4% and 98.7%, respectively; P<0.001 for both comparisons). Of the 196 patients in the pretrial prophylaxis cohort, 98 each were assigned to group 3 or group 4. The estimated mean annualized rate of treated bleeding events was 2.25 (95% CI, 1.37 to 3.71) in group 3, as compared with 4.90 (95% CI, 3.65 to 6.56) during the run-in phase (relative decrease, 54.0%; P = 0.006), and 1.78 (95% CI, 1.18 to 2.71) in group 4, as compared with 3.12 (95% CI, 2.25 to 4.32) (relative decrease, 42.8%; P = 0.006). Injection-site reactions were reported in 103 of 4005 injections (2.6%). No patient was reported to have a thromboembolic event or clinical evidence of neutralizing anti-Mim8 antibodies. Among patients with hemophilia A with or without inhibitors, Mim8 prophylaxis was superior to on-demand treatment and clotting factor concentrate prophylaxis regarding the annualized rate of treated bleeding events. (Funded by Novo Nordisk; FRONTIER2 ClinicalTrials.gov number, NCT05053139.).
 Adolescent Adult Aged Antibodies, Bispecific - administration & dosage Antibodies, Bispecific - adverse effects Blood Coagulation Factors - administration & dosage Child Drug Administration Schedule Factor VIII - administration & dosage Factor VIII - adverse effects Factor VIII - antagonists & inhibitors Factor VIII - immunology Factor VIIIa - administration & dosage Factor VIIIa - adverse effects Female Hemophilia A - blood Hemophilia A - complications Hemophilia A - drug therapy Hemophilia A - immunology Hemorrhage - blood Hemorrhage - epidemiology Hemorrhage - immunology Hemorrhage - prevention & control Humans Injections, Subcutaneous Isoantibodies - blood Isoantibodies - immunology Male Middle Aged Treatment Outcome Young Adult

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