- Phase 3 FRONTIER2 (n=254; 26-week) evaluated denecimig (Mim8), an FVIIIa-mimetic bispecific antibody, dosed once-monthly or once-weekly in haemophilia A patients age 12+ with or without inhibitors
- Once-monthly dosing reduced annualised bleeding rate ~99% vs on-demand and ~43% vs prior clotting-factor prophylaxis; once-weekly reduced ~96% vs on-demand and ~54% vs prior prophylaxis
- Safety: generally well tolerated, no thromboembolic events or neutralising anti-denecimig antibodies; injection-site reactions occurred in 10% of participants (2.6% of injections)
- Novo Nordisk submitted a BLA to the FDA for denecimig in September 2025; the FRONTIER program includes multiple trials (FRONTIER1-5)
Trial overview
FRONTIER2 is a phase 3, 26‑week trial of denecimig (Mim8), a subcutaneous FVIIIa‑mimetic bispecific antibody, in 254 patients aged ≥12 with haemophilia A, with or without FVIII inhibitors; 246 completed the main phase.
Dosing and endpoint
Patients received once‑monthly or once‑weekly denecimig; the primary endpoint was mean annualised bleeding rate (ABR) of treated bleeds versus prior clotting‑factor prophylaxis or on‑demand treatment.
Efficacy
Once‑monthly dosing reduced ABR ~99% versus on‑demand and ~43% versus prior prophylaxis; once‑weekly reduced ~96% versus on‑demand and ~54% versus prior prophylaxis. Zero treated bleeds occurred in 64–95% of denecimig recipients across arms; comparator arms had 0–37% zero treated bleeds (0% for on‑demand; 33% and 37% for the two pre‑study prophylaxis comparator groups).
Safety and population
Denecimig was generally well tolerated: no thromboembolic events or clinical evidence of neutralising anti‑denecimig antibodies were reported; injection‑site reactions occurred in 10% of participants (2.6% of injections). The cohort included 4 females, 66 adolescents (12–17), 212 with severe haemophilia A and 31 with FVIII inhibitors.
Regulatory status
A Biologics License Application for denecimig was submitted to the FDA in September 2025.
