Novo Nordisk has announced that phase 3b results from the FRONTIER5 study of investigational denecimig were published in the Journal of Thrombosis and Haemostasis. The 26-week results showed that a direct switch to the subcutaneous denecimig pen injector from the emicizumab vial and syringe injection system, without a washout period or a denecimig loading dose, was well tolerated with no unforeseen safety concerns in adolescents and adults living with hemophilia A (congenital factor VIII deficiency) with or without inhibitors.

Compared to their previous emicizumab vial and syringe system, most patients preferred the denecimig pen injector and found it easier to use, as measured by the Hemophilia Device Handling and Preference Assessment (HDHPA) as a supportive secondary endpoint. Additionally, exploratory results showed thrombin peak height increased into the normal range and was sustained over 26 weeks, with no clinical evidence of excessive clotting observed after the switch from emicizumab to denecimig across all dosing frequencies.

Stephanie Seremetis, Chief Medical Officer and CVP for Rare Disease, Novo, said, "What stands out from the published phase 3b data is the well-tolerated switch to denecimig along with the sustained increase in thrombin generation into the normal range. The positive device handling data and majority preference for our injection pen was equally encouraging, and a testament to Novo's intentional design process with the goal of providing this patient population additional options for administration."

In the open-label phase 3b FRONTIER5 safety study, 61 adults and adolescents aged 12 years and older with hemophilia A, with or without inhibitors, were enrolled and completed the 26-week treatment period. The primary safety endpoint of the study found that between week 0 and week 26 of treatment, there were 107 Treatment-Emergent Adverse Events (TEAEs) observed in 43 patients (70.5 percent), most of which were mild to moderate (98.1 percent). There were 24 TEAEs that were possibly/probably related to denecimig.

Denecimig safety was found to be consistent with findings previously shared from the FRONTIER research program. No thromboembolic events, hypersensitivity reactions, or TEAEs leading to discontinuation were observed, and there was no clinical evidence of neutralising anti-denecimig antibodies.

Hemophilia A is a rare, inherited bleeding disorder where a deficiency in clotting factor VIII hinders thrombin production, impairing the body's ability to make blood clots and stop bleeding.

A Biologics License Application (BLA) is currently under review with the US Food and Drug Administration (FDA) for denecimig as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A, with or without inhibitors, in once-weekly, once-every-two-weeks, or once-monthly dosing frequencies.

Allison P Wheeler, MD, University of Colorado School of Medicine, Aurora CO, said, "Switching to a new hemophilia treatment typically requires careful spacing between treatments to avoid creating a combined, additive effect on thrombin generation. Additionally, that transition period requires close monitoring and coordination to manage gaps in protection that could increase the risk of breakthrough bleeding. Crucially, patients in the FRONTIER5 study were able to safely switch directly to denecimig without waiting until emicizumab is completely cleared from their system, and without needing an initial loading dose to jump-start their new regimen."

A supportive secondary endpoint studied among 59 of the 61 enrolled patients showed most participants (98.3 percent) rated the denecimig injection pen as "easy" or "very easy" to use (Hemophilia Device Handling and Preference Assessment, HDHPA). Most patients (94.9 percent) reported that the denecimig injection pen was easier to use overall than their previous administration method and most patients (96.6 percent) preferred the denecimig injection pen to the previous administration method. Responses were similar across each dosage frequency.

An additional supportive secondary endpoint studied in 55 of the 61 enrolled patients found denecimig reduced treatment burden by an average (Standard Deviation [SD]) of 4.7 points (9.0) at week 26, from a baseline total score of 10.5 (10.2), based on the Hemophilia Treatment Experience Measure.

Data from an exploratory objective of FRONTIER5 showed denecimig increased thrombin generation, a measure of blood clotting function, to levels in the normal range after switching from emicizumab. The increase was sustained over the 26-week study period without any clinical evidence of synergistic thrombin peak height effect or excessive clotting across all dosing frequencies. Denecimig also reached steady-state plasma concentrations by week 16 without a loading dose.