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

Background: Denecimig (Mim8) is a next-generation activated factor (F)VIII mimetic bispecific antibody developed for subcutaneous prophylaxis in patients with hemophilia A (HA). Objectives: This study evaluated 52-week outcomes with denecimig in children from the phase 3 FRONTIER3 study (NCT05306418). Methods: Children aged 1 to 11 years with HA with or without FVIII 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 end point was the number of treatment-emergent adverse events. Assessed secondary outcomes included the number of treated bleeds and subtypes, injection-site reactions, antidenecimig antibodies, and caregiver-reported outcomes. Results: All 70 enrolled participants completed Parts 1 and 2 of the study. During Part 2, 38 participants continued QW and 32 switched to QM. All treatment-emergent adverse events were mild/moderate, and none led to discontinuation. No thromboembolic events or clinical evidence of neutralizing antibodies were reported; injection-site reactions were infrequent (∼1% of injections). Estimated mean annualized 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% to 88% of participants had zero treated bleeds; no bleeds were reported in inhibitor-positive children with HA with inhibitors. All 10 baseline target joints resolved. Caregivers reported reduced treatment burden and improved physical functioning, and 98% of caregivers preferred denecimig to prior therapy. Conclusion: 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.