Experimental treatment maintains low bleed rates in hemophilia A
Extension study reports reduced treatment burden across dosing schedules
Written by |
- Denecimig (Mim8) is an investigational antibody therapy being developed for people with hemophilia A.
- In an ongoing extension study, denecimig maintained low bleeding rates across age groups, inhibitor status, and dosing schedules.
- Safety findings were consistent with earlier FRONTIER trials, and Novo Nordisk has applied for FDA approval of the therapy.
Denecimig (Mim8), an investigational antibody therapy being developed by Novo Nordisk, continued to maintain low bleeding rates in children, adolescents, and adults with hemophilia A, with safety findings consistent with earlier studies, regardless of inhibitor status or dosing schedule.
That’s according to interim data from FRONTIER4 (NCT05685238), an ongoing, open-label extension study evaluating the long-term safety and efficacy of once-weekly, once-every-two-weeks, and once-monthly denecimig as prophylactic (preventive) treatment in people aged 1 year and older with or without inhibitors.
FRONTIER4 tracks denecimig’s longer-term effects
Participants who completed earlier FRONTIER studies were invited to continue receiving the therapy in FRONTIER4. The study continues to recruit participants at sites worldwide.
The interim findings were presented at this year’s International Society on Thrombosis and Haemostasis (ISTH) Congress, held July 11-15 in Paris.
“The positive safety and efficacy findings from FRONTIER4 reinforce denecimig’s potential as a preventive treatment option for children, adolescents, and adults with hemophilia A, regardless of their inhibitor status or the dosing frequency used,” Martin Holst Lange, PhD, chief scientific officer and executive vice president of Research and Development at Novo Nordisk, said in a company press release.
“The breadth and totality of our data presented at ISTH reflect Novo Nordisk’s commitment to advancing treatment innovation to address the diverse needs of people living with hemophilia,” Holst Lange said.
Hemophilia A is caused by mutations in the F8 gene that result in little or no working clotting factor VIII (FVIII). Without enough functional FVIII, blood does not clot properly, increasing the risk of prolonged or spontaneous bleeding, particularly into the joints.
Factor replacement therapies, which provide the body with a working version of FVIII, are used to prevent and treat bleeds. But some patients develop inhibitors, or neutralizing antibodies that target the replacement FVIII and may reduce its effectiveness.
Denecimig is designed to overcome that challenge. Given by injection under the skin, the investigational therapy is a bispecific antibody designed to prevent or reduce bleeding by mimicking the activity of activated FVIII and supporting the body’s ability to form blood clots. Because its activity does not depend on replacement FVIII, denecimig is being developed for people both with and without inhibitors.
Earlier trials found low bleed rates with denecimig
Previous Phase 3 studies have supported that potential. In FRONTIER2 (NCT05053139), weekly and monthly preventive treatment with denecimig was more effective than on-demand or standard preventive treatments at reducing bleeding episodes in adults and adolescents with hemophilia A, regardless of inhibitor status.
Similarly, interim data from FRONTIER3 (NCT05306418) showed that weekly and monthly injections of the therapy maintained low bleeding rates and were generally well tolerated in children with hemophilia A, regardless of inhibitor status.
The ongoing FRONTIER4 study is designed to determine whether those benefits are maintained over longer treatment periods. In this study, denecimig is given under the skin using a pen injector. FRONTIER4 plans to enroll up to 451 people with hemophilia A, including those who previously participated in one of the FRONTIER studies and chose to continue receiving denecimig.
The interim analysis included data from 426 participants: 365 adolescents and adults who had been observed in FRONTIER4 for a median of six months, and 61 children who had been observed for about four months. Participants had previously received denecimig in an earlier FRONTIER study before entering the extension.
Safety findings were consistent with those reported in earlier FRONTIER trials. Mild, short-lived injection-site reactions were reported after 1.8% of injections in adolescents and adults and 2% of injections in children. Researchers also found no clinical evidence of neutralizing antibodies against denecimig.
The therapy also maintained low annualized bleeding rates (ABRs), which estimate how many bleeding episodes a person would experience in one year. Across all dosing schedules and regardless of inhibitor status, the estimated mean ABR was 0.75 among adolescents and adults and 0.37 among children. Overall, 71% of adolescents and adults and 89% of children experienced no treated bleeding episodes while receiving denecimig.
Patients report less pain and treatment burden
Patient-reported outcomes also suggested that benefits seen in earlier FRONTIER studies were sustained over time. Participants age 12 and older continued to report less joint pain, while people across all age groups reported a lower treatment burden. Among 185 participants who assessed the pen injector, 94.1% found it easy or very easy to use, while 89.7% found it quick or very quick to prepare and administer.
Additional analyses of data from FRONTIER studies also found that, in participants age 12 and older, preventive treatment with denecimig increased thrombin generation — a measure of the body’s ability to form blood clots — to within the normal reference range, without evidence of an excessive clotting response.
“When managing a chronic condition like hemophilia A, it’s important that treatments are evaluated over the long-term and also offer dosing optionality,” said Guy Young, MD, director of the Hemostasis and Thrombosis Center at Children’s Hospital Los Angeles. “These data suggest denecimig, which has delivered consistent results across the entire FRONTIER program, has the potential to have a truly meaningful impact for a diverse array of people with hemophilia A.”
Based on results from FRONTIER2 and FRONTIER3, together with findings from the ongoing FRONTIER4 extension study, Novo Nordisk has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of denecimig as a preventive treatment for people with hemophilia A, with or without inhibitors.
Leave a comment
Fill in the required fields to post. Your email address will not be published.