Novo Nordisk: Denecimig tolerated after direct switch from emicizumab in FRONTIER5

Study population and design

FRONTIER5 was an open‑label phase 3b safety study of a direct switch from emicizumab to subcutaneous denecimig in 61 adolescents and adults aged 12 years and older with haemophilia A, with or without inhibitors. The study evaluated a 26‑week treatment period without a washout or denecimig loading dose.

Safety outcomes

Between Week 0 and Week 26 there were 107 treatment‑emergent adverse events (TEAEs) in 43 patients (70.5%), of which 98.1% were mild or moderate. Twenty‑four TEAEs were judged possibly or probably related to denecimig. No thromboembolic events, hypersensitivity reactions, or TEAEs leading to discontinuation were observed, and no clinical evidence of neutralizing anti‑denecimig antibodies was reported.

Device performance and patient experience

Among 59 respondents to the Hemophilia Device Handling and Preference Assessment (HDHPA), 98.3% rated the denecimig pen as “easy” or “very easy” to use; 94.9% said it was easier overall than their prior method and 96.6% preferred the pen. Hemo‑TEM scores (N=55) showed a mean reduction in treatment burden of 4.7 points from a baseline total score of 10.5 at Week 26.

Pharmacodynamics and regulatory status

Exploratory data showed mean thrombin peak height rose from cohort baselines (overall Week 0 ~25.5 nmol/L) to Week 26 (overall ~39.8 nmol/L), with a mean within‑subject percent change of 78.8% and no clinical evidence of excessive clotting. Denecimig reached steady‑state plasma concentrations by Week 16 without a loading dose. A Biologics License Application for denecimig as routine prophylaxis is under review by the US FDA for once‑weekly, once‑every‑two‑weeks and once‑monthly dosing.