Denecimig (Mim8) prophylaxis once every 2 weeks for hemophilia A with or without inhibitors: 26-week results from...

Denecimig (Mim8) is a next-generation, activated factor VIII mimetic, fully human bispecific immunoglobulin G4 antibody in development for subcutaneous prophylaxis in bleeding episodes, for patients with hemophilia A (HA) with/without inhibitors. FRONTIER4 is an open-label extension study to assess the safety and efficacy of denecimig. Here we present an interim analysis of patients receiving denecimig once every 2 weeks (Q2W) in FRONTIER4. Patients with HA aged ≥12 years who had participated in the denecimig phase 2 study and ≥12 weeks of its extension and entered arm 1 of the FRONTIER4 phase 3 study received denecimig Q2W for 26 weeks using a tiered dosing approach according to body weight range. The primary end point was the number of treatment-emergent adverse events (TEAEs); secondary end points included injection site reactions, occurrence of anti-denecimig antibodies, denecimig plasma concentrations, and number of treated bleeds. Thirty-seven patients were enrolled who received denecimig for a mean of 1.73 years in the phase 2 study. Sixty TEAEs were reported in 20 patients. Most TEAEs were mild/moderate in severity (98.3%), unlikely to be related to denecimig (75.0%), and resolved during the time frame of this analysis (90.0%). No TEAEs led to permanent discontinuation of denecimig, and none were fatal. Two patients reported 14 injection site reactions. Denecimig plasma concentrations were stable through week 26. The estimated mean annualized bleeding rate was 0.38 bleeds per patient year. Most patients experienced zero treated bleeds (83.8%). In summary, denecimig administered Q2W was well tolerated, with few patients experiencing treated bleeds and no safety concerns. This trial was registered at www.clinicaltrials.gov as NCT05685238.