Denecimig (Mim8) prophylaxis over 52 weeks in adolescents and adults with hemophilia A: FRONTIER2 extension study

Denecimig (Mim8) is a fully human, activated factor VIII (FVIII) mimetic bispecific antibody in development for subcutaneous prophylaxis to prevent bleeding in persons with hemophilia A (HA).

This study aimed to report the efficacy and safety of denecimig over 52 weeks in adolescents and adults from FRONTIER2 (NCT05053139).

Males and females (aged ≥12 years) with HA (any severity), with or without inhibitors, were enrolled. In the 26-week main phase, patients previously treated on-demand were randomized to continue on-demand treatment (arm 1) or receive denecimig injections once every week (QW; arm 2a) or once every month (QM; arm 2b); patients previously receiving clotting factor concentrate prophylaxis were randomized to receive denecimig QW (arm 3) or QM (arm 4). In the 26-week extension, patients in arm 1 switched to denecimig QW or QM; other arms followed the same dosing frequency. Annualized bleeding rate (ABR) of treated bleeds was estimated using a negative binomial model.

In the main phase, 281 patients were randomized; 272 entered the extension. Estimated mean ABR in the extension for arm 1 was 0.67 (QW) and 0.79 (QM). Mean ABR over 52 weeks was 0.37, 0.21, 2.02, and 1.65 in arms 2a, 2b, 3, and 4, respectively. Most baseline target joints resolved. No hypersensitivity reactions, thromboembolic events, or clinical evidence of neutralizing anti-denecimig antibodies occurred. Injection-site reactions occurred in 1.81% and 1.34% of patients administered denecimig QW and QM injections, respectively. Patient-reported physical function improved; treatment burden and joint pain was reduced.

Denecimig maintained low ABRs over 52 weeks, was well tolerated, and improved patient-reported outcomes in adolescents and adults with HA with or without inhibitors.