Denecimig (Mim8) prophylaxis in children with hemophilia A with or without factor VIII inhibitors

Background Denecimig (Mim8) is a next-generation activated factor VIII mimetic bispecific antibody developed for subcutaneous prophylaxis in patients with haemophilia A (HA). Objectives To evaluate 52-week outcomes with denecimig in children from the phase 3 FRONTIER3 study (NCT05306418). Methods Children aged 1–11 years with HA, with or without factor VIII inhibitors, received subcutaneous denecimig once-every-week (QW) for 26 weeks (Part 1). In Part 2, caregivers chose to continue QW or switch to once-every-month (QM) dosing for 26 weeks. Primary endpoint: number of treatment-emergent adverse events (TEAEs). Assessed secondary outcomes included the number of treated bleeds and subtypes, injection-site reactions, anti-denecimig antibodies and caregiver-reported outcomes. Results All 70 enrolled participants completed Parts 1 and 2. During Part 2, 38 participants continued QW and 32 switched to QM. All TEAEs were mild/moderate, and none led to discontinuation. No thromboembolic events or clinical evidence of neutralising antibodies were reported; injection-site reactions were infrequent (∼1% of injections). Estimated mean annualised bleeding rates for treated bleeds were 0.53 (Part 1, QW), 0.42 (Part 2, QW), 0.25 (Part 2, QM) and 0.50 (Parts 1 and 2, QW); 74–88% of participants had zero treated bleeds; no bleeds were reported in inhibitor-positive children. All 10 baseline target joints resolved. Caregivers reported reduced treatment burden and improved physical functioning, and 98% of caregivers preferred denecimig to prior therapy. Conclusions Over 52 weeks, denecimig prophylaxis was well tolerated with no safety concerns and provided robust bleed protection, reduced treatment burden and improved overall health-related quality of life in children with HA.