RARE Daily

Novo Nordisk’s Hemophilia A Candidate Hits Primary Endpoint in Phase 3 Study

May 14, 2024

Rare Daily Staff

Novo Nordisk reported strong positive results from the pivotal study of its experimental, next-generation prophylaxis for the rare bleeding disorder hemophilia A

Hemophilia is a rare inherited bleeding disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding. Due to the nature of hemophilia being a rare x-linked recessive disorder, it often presents differently in males compared to females, with approximately 88 percent of people diagnosed with hemophilia worldwide being male.

There are different types of hemophilia, which are characterized by the type of clotting factor protein that is defective or missing. Hemophilia A is caused by a missing or defective clotting factor VIII (FVIII). Some people with hemophilia may also develop inhibitors, which are an immune system response to the clotting factors in replacement therapy that cause treatment to stop working. Currently, it is estimated that up to 30 percent of people living with hemophilia A have inhibitors.

Mim8 is a next-generation factor VIIIa mimetic bispecific antibody delivering sustained hemostasis for once-weekly or once-monthly prophylaxis for people living with hemophilia A, with and without inhibitors. Administered subcutaneously, Mim8 bridges factor IXa/X (FIXa/FX) together upon activation, thereby replacing missing FVIII, which effectively restores the body’s thrombin generation capacity, helping blood to clot.

FRONTIER 2 trial, a pivotal phase 3a, 26-week open-label, randomized, controlled, multi-arm trial in 254 people with hemophilia A. The trial investigated the efficacy and safety of once-weekly and once-monthly subcutaneous Mim8 versus no prophylaxis and versus prior coagulation factor prophylaxis treatment in people aged 12 years or older with hemophilia A with or without inhibitors.

The trial achieved its co-primary endpoints by demonstrating a statistically significant and superior reduction of treated bleeding episodes with both once-weekly and once-monthly Mim8 versus no prophylaxis treatment and prior coagulation factor prophylaxis treatment.

In people with no prior prophylaxis treatment, once-weekly and once-monthly Mim8 demonstrated superior reductions of 97 percent and 99 percent in treated bleeds, respectively, compared to those who received no prophylaxis treatment. In addition, 86 percent of people treated with once-weekly Mim8 and 95 percent of those treated with once-monthly Mim8 experienced zero treated bleeds, compared to zero percent of those treated with no prophylaxis.

In the intra-patient analysis in people with prior coagulation factor prophylaxis, Mim8 demonstrated reductions in treated bleeds of 48 percent in once-weekly cohort and 43 percent in the once-monthly cohort compared to prior coagulation factor prophylaxis. Additionally, 66 percent of people treated with once-weekly Mim8 and 65 percent of people treated with once-monthly Mim8 experienced zero treated bleeds.

In the trial, Mim8 appeared to have a safe and well-tolerated profile in line with previous trials. No deaths or thromboembolic events were reported in the trial.

Contingent on regulatory interactions, Novo Nordisk aims to submit Mim8 for the first regulatory approval towards the end of 2024. Data from the phase 3 FRONTIER program, including FRONTIER 2 will be disclosed at upcoming congresses and in publications in 2024 and 2025.

“We are very pleased with the positive results from the FRONTIER 2 clinical trial. These data demonstrate the ability of Mim8 to prevent bleeding episodes effectively and safely in people with hemophilia A, regardless of their dosing frequency,” said Martin Holst Lange, executive vice president for development at Novo Nordisk. “Given the differing needs of people living with hemophilia A, a convenient once-weekly or once-monthly dosing provides optionality and flexibility for people living with hemophilia A with or without inhibitors.”

Photo: Martin Holst Lange, executive vice president for development at Novo Nordisk

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