Antibody therapy Mim8 seen effective in hemophilia A children
Interim Phase 3 trial data show treatment well tolerated
Antibody therapy Mim8 (denecimig) was well tolerated and provided effective bleed control in children with hemophilia A regardless of inhibitor status.
That’s according to interim data from the now-complete Phase 3 FRONTIER3 study (NCT05306418), which enrolled children ages 1-11. These findings were consistent with recent data from the Phase 3 FRONTIER2 trial (NCT05053139), in which Mim8 led to significant bleed reductions in adults and adolescents with hemophilia A.
The new data were presented at the Congress of the European Association for Haemophilia and Allied Disorders, held Feb. 4-7 in Milan.
“The FRONTIER3 interim analysis data are encouraging for families with young children and indicate that Mim8 could offer an efficacious, convenient, flexible dosing option for children, helping to reduce the treatment burden so families can live more normal lives,” Johnny Mahlangu, the study’s lead investigator and director of the Haemophilia Comprehensive Care Centre at Charlotte Maxeke Johannesburg Hospital, said in a company press release.
FRONTIER2 and FRONTIER3 are two of the studies in Novo Nordisk’s FRONTIER trial program that’s investigating Mim8 as a prophylactic (preventive) hemophilia A treatment. Data from these studies may support regulatory applications for Mim8’s approval, which the company expects to submit this year. Novo Nordisk said it plans to present additional data from the FRONTIER program in publications and at scientific conferences this year and next.
Designed for patients with or without inhibitors
Hemophilia A patients lack factor VIII (FVIII), a blood clotting protein, which leaves them susceptible to excessive and uncontrolled bleeding episodes.
Replacement therapies that provide the body with a version of FVIII are used to prevent and treat bleeds. But some patients develop inhibitors, or neutralizing antibodies against FVIII that can render these treatments less effective.
Administered via subcutaneous (under-the-skin) injection, Mim8 is designed to bypass the need for FVIII products by mimicking the clotting protein’s function in the body. It’s therefore expected to be able to safely prevent bleeds in people with and without inhibitors. It is an antibody that simultaneously binds to two other blood clotting proteins — factor IX and factor X — which FVIII is normally responsible for bridging together to promote blood clotting.
FRONTIER3 enrolled 70 hemophilia A patients, ages 1-11, with or without inhibitors. In the first part of the study, all received weekly injections of Mim8 for 26 weeks, or about six months. Participants were then offered the option of continuing to receive weekly injections or switching to monthly injections for another six months in the second part of the study.
The study’s main goal was to evaluate the therapy’s safety, and Novo Nordisk reported that the treatment was well tolerated with no major safety concerns.
Lower bleed rates
During the study’s first part, the estimated mean annualized bleed rate (ABR) — the number of bleeds occurring in a year — for bleeds requiring treatment was 0.53, and the median ABR was 0. Three-quarters of the children (74.3%) had no treated bleeds, including all 14 with inhibitors.
Among the 36 children who were treated with other prophylactic therapies during a six-month run-in period before the study, the mean ABR for treated bleeds was reduced by more than 60% on Mim8 compared with prior prophylaxis.
The treatment was similarly effective in children ages 1-5 and in those ages 6-11.
After finishing the study’s first part, 55% of participants opted to stay on weekly dosing for part 2, and 45% switched to monthly dosing. Initial findings from the study’s second part generally reflected that bleed rates remained low even among those who switched to monthly dosing.
Nearly all caregivers (98%) indicated they preferred Mim8 to prior treatments, including 73% who said they preferred it “very strongly,” according to Novo Nordisk. Other patient- and caregiver-reported outcome measures also tended to indicate improvements in physical function and life quality relative to the period before the study started.
“The FRONTIER3 data represent another step forward in our ambition to provide treatment options that place equal focus on safety and efficacy without requiring a compromise on treatment administration and quality of life,” said Ludovic Helfgott, executive vice president for rare disease at Novo Nordisk. “Mim8 is designed with the aim to offer treatment flexibility based on individual lifestyles, so it is encouraging to see that patients and caregivers in these analyses prefer Mim8 over their previous treatment.”
Other trials in the FRONTIER program include FRONTIER 4 (NCT05685238), an open-label extension study where participants who completed previous studies can continue to receive Mim8 long-term, and the FRONTIER 5 trial (NCT05878938), which tested whether it was safe for patients using Hemlibra to switch to Mim8.
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