Positive Early Results of Mim8 Pave Way for Testing in Phase 3 Trials
Therapy found safe, well-tolerated to support future hemophilia A clinical trials
Mim8, an investigational therapy to prevent bleeding episodes in people with hemophilia A, is safe and well-tolerated at multiple doses, according to data from the Phase 1/2 FRONTIER1 trial.
The therapy also showed signs of efficacy, with most patients given higher doses experiencing no bleeds during treatment.
“We are encouraged by the first phase 1 & 2 data from FRONTIER1,” Jerzy Windyga, MD, a professor at the Institute of Hematology and Transfusion Medicine in Poland, and the study’s principal investigator, said in a press release.
“Mim8 demonstrated clinical proof-of-concept and no safety signals or signs of exaggerated coagulation [blood clotting] were seen, which supports the further clinical development of Mim8 in people living with haemophilia A in phase 3 clinical trials,” Windyga said.
The data were presented at the International Society of Thrombosis and Haemostasis Annual Congress, held July 9–13, in London, in a presentation titled “A Phase 1/2 Dose Escalation Study of a Novel Factor VIIIa Mimetic Bispecific Antibody, Mim8, for Evaluation of Safety, Pharmacokinetics, and Efficacy.”
Hemophilia A is characterized by a missing or defective blood clotting protein, called factor VIII (FVIII), leading to symptoms such as excessive and uncontrolled bleeding. Patients with the disorder are usually treated with replacement therapy, which provides the missing FVIII via into-the-vein infusions.
But some patients develop inhibitors, or neutralizing antibodies against FVIII, limiting the effectiveness of replacement therapy.
Mim8 is a next-generation therapy developed by Novo Nordisk to bypass the need for FVIII by mimicking its activity. Delivered as an under-the-skin injection, Mim8 is composed of an antibody that bridges together two other clotting factors — factor IXa and factor X — mimicking the role that FVIII usually plays in the body. This stimulates production of thrombin, an enzyme that helps blood to clot.
FRONTIER1 Phase 1/2 clinical trial results
The FRONTIER1 trial (NCT04204408) is investigating the tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of Mim8 in healthy participants and multiple ascending doses in people with hemophilia A with or without inhibitors. Pharmacokinetics assesses how a medicine moves into, through, and out of the body, while pharmacodynamics refers to a treatment’s effects on the body.
The single-ascending dose part (Phase 1) involved 48 healthy adult males, ages 18–45, who were given a single, under-the-skin injection of Mim8 at doses targeting blood concentrations of 0.05 micrograms per milliliter (mcg/mL) to 3 mcg/mL, or a placebo.
Data from that part showed that Mim8 was well-tolerated, with no serious adverse events reported.
In the multiple-ascending dose portion (Phase 2), 42 males with severe hemophilia A, ages 12–64, were randomized to receive either weekly or monthly doses of Mim8 over 12 weeks. The therapy was given at weekly doses targeting blood concentrations of 1, 3, 9 or 20 mcg/mL. The monthly treatment targeted blood levels of 9 mcg/mL.
Presented data concerned 32 patients across the three lowest weekly dosing groups and the monthly dosing group.
Mim8 was well-tolerated at all tested doses, regardless of whether a patient did or did not have inhibitors. No blood clots or other treatment-related serious adverse events were reported, and no participants developed antibodies against the treatment.
Of 15 reported bleeds in eight patients, 13 occurred in patients who received the lowest dose of Mim8, with bleeds reported in six out of seven people in that group. The remaining two bleeds occurred in the higher weekly dosing groups, and no bleeds were reported in any participants who received the therapy monthly.
After the 12-week period, participants continued on the same treatment regimen into an extension phase.
“The needs of each person living with haemophilia are individual, complex and changing, meaning that in its treatment there is no ‘one size fits all’. The results from the FRONTIER1 study present an opportunity to develop an alternative treatment for people with haemophilia A who may benefit from less frequent administration,” Stephanie Seremetis, MD, chief medical officer of rare blood disorders at Novo Nordisk, said in an emailed statement to Hemophilia News Today.
“While Mim8 is still in the early stages of clinical study programme, [and] therefore we are unable to speculate about what the results mean for people living with haemophilia or the medical community, the data enable us to move into phase 3 clinical development, which is due to commence in [the fourth quarter of 2022],” added Seremetis.
The FRONTIER clinical program is using an accelerated trial design to shorten the time between Phase 2 and 3 clinical testing, according to the company.
A Phase 3 trial (NCT05053139) investigating the efficacy of weekly or monthly Mim8 injections in people with hemophilia A, with or without inhibitors, is recruiting up to 244 participants, 12 and older, at several sites globally.
A similar Phase 3 trial (NCT05306418) will test the treatment in about 70 children under age 12. That trial is currently recruiting participants at a study location in Poland.
Dosing in a Phase 3 study is expected to start by the end of the year.
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