Mim8 for hemophilia

Last updated July 24, 2024, by Andrea Lobo, PhD
Fact-checked by Inês Martins, PhD

What is Mim8 for hemophilia?

Mim8 (denecimig) is an investigational therapy being tested as a way to prevent or reduce the frequency of bleeding episodes in people with hemophilia A, with or without neutralizing antibodies (inhibitors).

Administered via routine subcutaneous, or under-the-skin, injections in clinical trials, the prophylactic therapy is being developed by Novo Nordisk, which announced plans to submit a regulatory application for Mim8’s approval in late 2024.

Therapy snapshot

How does Mim8 work in hemophilia?

Hemophilia A is caused by mutations in the F8 gene, which contains instructions for making the essential clotting protein called factor VIII (FVIII). When FVIII is missing or defective, the blood cannot clot properly, and patients may experience prolonged bleeding episodes that can be hard to control.

Standard treatment for people with hemophilia A usually includes factor replacement therapies, which routinely provide patients with a functional FVIII to control or prevent bleeding episodes. However, some patients develop neutralizing antibodies against the delivered clotting factor, which can limit the treatment’s efficacy.

Normally, FVIII binds to both factor IX (FIX) and factor X (FX) to initiate the signaling cascade responsible for blood clotting.

Mim8 is a next-generation bispecific antibody designed to mimic the function of the missing clotting factor. It also binds to both FIX and FX, stimulating the production of thrombin, an enzyme that helps the blood to clot.

The treatment is expected to prevent or reduce bleeding episodes in people with hemophilia A. Because it does not involve giving patients an external source of FVIII, Mim8 can be administered to people with inhibitors.

Notably, Mim8 has a similar mechanism as the approved hemophilia A treatment Hemlibra (emicizumab), but animal studies suggest it is better at promoting thrombin production and clot formation.

How will Mim8 be administered in hemophilia?

In Phase 3 trials involving people with hemophilia A, Mim8 has been administered via weekly or monthly subcutaneous injections. The treatment’s recommended regimen and dosing schedule, however, will not be known unless it goes on to gain regulatory approval.

Mim8 in hemophilia clinical trials

Early clinical trials — 4882 (NCT05127473) and FRONTIER 1 (NCT04204408) — demonstrated that Mim8 was generally safe and well tolerated in healthy volunteers and hemophilia A patients. FRONTIER 1, a Phase 2 study, also supported the therapy working as intended in patients.

Findings led Novo Nordisk to launch two Phase 3 clinical trials as part of its FRONTIER development program, both of which are testing Mim8 as a prophylactic, or preventive, treatment for people with hemophilia A with or without inhibitors.

FRONTIER 2

A global and pivotal Phase 3 trial (NCT05053139), called FRONTIER 2, is evaluating the medication in 254 adults and adolescents, ages 12 and older. Participants were randomly assigned to either weekly or monthly subcutaneous injections of Mim8 or to continue with their routine preventive or on-demand FVIII replacement treatment for 26 weeks, or about six months.

All then were invited to enter an open-label extension and be treated with Mim8, either weekly or monthly based on the investigators’ assessment, for another 26 weeks.

Top-line trial data demonstrated that, in patients who were not using prophylactic treatments prior to enrollment, once-weekly injections of Mim8 reduced the number of treated bleeds by 97%, and once-monthly dosing lowered that number by 99%.  More than 85% of these patients experienced no bleeds requiring treatment, compared with 0% among those not receiving prophylaxis.

Patients using preventive FVIII therapies prior to enrollment continued to do so for at least 26 weeks in a run-in period, before starting with Mim8 for another 26 weeks. Compared with the run-in period, the number of their treated bleeds fell by 48% while on weekly Mim8, and by 43% with monthly treatment. Moreover, at least 65% of these patients had no treated bleeds across the 26 weeks they were receiving Mim8.

Mim8 was found to be safe and well tolerated, in line with that seen in previous trials. No deaths or blood clotting events were reported.

FRONTIER 2 is expected to conclude in November 2024.

FRONTIER 3

The Phase 3 and global FRONTIERS 3 trial (NCT05306418) is assessing Mim8’s safety and efficacy in children with hemophilia A, ages 1 to 11, with or without inhibitors. All are being treated once weekly for at least 26 weeks, after which they can choose to continue on a weekly treatment regimen or switch to once-monthly treatment for another 26 weeks.

The trial’s main goal is to determine the treatment’s safety, as measured by the number of adverse events. Secondary goals include the number of treated bleeding episodes, treatment burden and preference, and quality of life.

FRONTIER 3 is expected to conclude in April 2025.

FRONTIER 4 extension study

Participants who completed the Phase 2 and 3 FRONTIER studies may continue to be treated with Mim8 in a long-term and open-label extension study called FRONTIER 4 (NCT05685238). The study started in 2023 and is expected to continue for up to 5.5 years.

FRONTIER 5 switching study

Another ongoing and global Phase 3 study, called the FRONTIER 5 trial (NCT05878938), is assessing whether it is safe for patients on Hemlibra to switch to Mim8. The trial has enrolled about 48 adults and adolescents, ages 12 and older, who were using Hemlibra for at least two months before screening and moving to Mim8 for 26 weeks. The investigative antibody here is being given using a prefilled pen injector and could be self administered, with once weekly, once every two weeks, and once monthly dosing options.

In addition to safety, researchers will examine patient preference and treatment burden.

Common side effects of Mim8

Data still are limited regarding the safety profile of Mim8 in people with hemophilia A. Based on findings in an earlier Phase 2 trial, the most common side effects that patients may experience are:

• allergic reactions
• injection site reactions.

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