Novo Nordisk’s denecimig shows positive long-term safety and efficacy results in Phase 3 haemophilia A FRONTIER extension study at ISTH 2026

Novo Nordisk has unveiled new findings from the Phase 3 FRONTIER4 extension study, which is assessing the long-term safety and efficacy of investigational denecimig (Mim8) subcutaneous prophylaxis in children, adolescents, and adults with haemophilia A with or without inhibitors, evaluated across once-monthly, once-every-two-weeks, and once-weekly administration. These results and additional data from across Novo Nordisk’s haemophilia portfolio were shared at the International Society on Thrombosis and Haemostasis Congress in Paris.

“The positive safety and efficacy findings from FRONTIER4 reinforce denecimig’s potential as a preventive treatment option for children, adolescents, and adults with hemophilia A, regardless of their inhibitor status or the dosing frequency used,” said Dr. Martin Holst Lange, Chief Scientific Officer and Executive Vice President, Research and Development, Novo Nordisk. “The breadth and totality of our data presented at ISTH reflect Novo Nordisk’s commitment to advancing treatment innovation to address the diverse needs of people living with hemophilia.”

The interim analysis of the open-label Phase 3 FRONTIER4 long-term safety and efficacy study drew on data from 426 people with haemophilia A aged one and older receiving denecimig prophylaxis, encompassing 365 adults and adolescents and 61 children. On the primary safety endpoint, denecimig performed in a manner consistent with findings previously reported across the FRONTIER programme. Injection site reactions were noted at low rates in both children and adults and adolescents, with all events mild and transient in nature. No clinical evidence of neutralising antibodies emerged. Secondary efficacy endpoints showed estimated mean annualised bleeding rates in line with earlier FRONTIER findings across all dosing regimens and regardless of inhibitor status. Across all doses, approximately 71% of adults and adolescents and 89% of children experienced zero treated bleeds while on denecimig.

An interim review of exploratory patient-reported outcomes from FRONTIER4 confirmed that gains seen in prior FRONTIER trials were sustained over the longer term across all dosing frequencies examined, including improvements in joint pain in those aged 12 and above and a reduction in treatment burden across all age groups from one year upward. Across all ages and dosing schedules, 94.1% of 185 participants found the denecimig pen-injector easy or very easy to handle, and 89.7% found it quick or very quick to prepare and administer.

New post hoc analyses in participants aged 12 and above with available thrombin generation data from the Phase 3 FRONTIER2 and FRONTIER5 studies found that denecimig prophylaxis brought thrombin generation, a measure of the blood’s capacity to form clots, into the normal reference range in adolescents and adults without producing an excessive response. These findings add further weight to the body of evidence building across denecimig’s clinical programme.

Novo Nordisk submitted a Biologics License Application for denecimig to the US Food and Drug Administration in September 2025.

“When managing a chronic condition like hemophilia A, it’s important that treatments are evaluated over the long-term and also offer dosing optionality,” said Guy Young, MD, Director, Hemostasis and Thrombosis Center at Children’s Hospital, Los Angeles. “These data suggest denecimig, which has delivered consistent results across the entire FRONTIER program, has the potential to have a truly meaningful impact for a diverse array of people with hemophilia A.”

Alongside the denecimig data, Novo Nordisk also presented first-time findings from the Phase 3 open-label concizumab explorer10 trial, which examined the efficacy and safety of concizumab prophylaxis in 24 children under the age of 12 living with haemophilia A or B with inhibitors. Within the trial, the estimated mean annualised bleeding rate on concizumab prophylaxis came in at 2.08, compared to 11.51 for the same patients on prior on-demand treatment, representing an 82% reduction. The majority of participants reported at least one on-treatment adverse event, most of which were mild in severity and resolved fully. Injection site reactions were infrequent, and serious adverse events were reported in 29% of participants.

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Related Topics and Keywords

haemophilia A, Novo Nordisk, Phase 3 trial