Novo Nordisk: denecimig (Mim8) shows positive long-term Phase 3 FRONTIER4 results in haemophilia A

Study and population

The interim FRONTIER4 long-term safety and efficacy study evaluated denecimig prophylaxis in 426 people with haemophilia A aged 1 year and older who continued from prior FRONTIER trials. Dosing frequencies studied included once-weekly, once-every-two-weeks and once-monthly; median observation periods were 0.50 years for adults/adolescents and 0.33 years for children.

Safety

For the primary endpoint, safety findings were consistent with prior FRONTIER data. Injection-site reactions were reported at low rates (2.0% of injections in children; 1.8% in adolescents and adults), were mild and transient, and no clinical evidence of neutralising antibodies was observed.

Efficacy and thrombin generation

Estimated mean annualised bleeding rates (ABRs) were 0.75 (95% CI 0.60–0.93) for adults/adolescents and 0.37 (95% CI 0.17–0.76) for children, irrespective of dosing regimen or inhibitor status. Across doses, ~71% of adults/adolescents and 89% of children experienced zero treated bleeds. Post hoc analyses from FRONTIER2, FRONTIER4 and FRONTIER5 showed denecimig restored thrombin generation into the normal reference range in adolescents and adults without an excessive response.

Patient-reported outcomes and device

Exploratory PROs were maintained long term across dosing frequencies, including improved joint pain in people aged ≥12 and reduced treatment burden in those aged ≥1. Of 185 participants, 94.1% rated the pen-injector easy or very easy to use and 89.7% rated it quick or very quick to prepare and inject.

Paediatric concizumab data

Separate explorer10 phase 3 data in 24 children <12 with haemophilia A or B with inhibitors reported mean ABR on concizumab prophylaxis of 2.08 versus 11.51 on prior on-demand treatment (ABR ratio 0.18), an 82% reduction; most adverse events were mild and injection-site reactions were infrequent.