Marstacimab for hemophilia
Last updated May 15, 2024, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
What is marstacimab for hemophilia?
Marstacimab, formerly known as PF-06741086, is an antibody-based therapy Pfizer is developing as a prophylactic treatment to prevent or reduce the frequency of bleeding episodes in people with hemophilia A or B. The once weekly therapy is administered via an under-the-skin, or subcutaneous, injection.
The therapy is up for approval in the U.S. and the European Union as a treatment for hemophilia A or B in patients who don’t have inhibitors, which are neutralizing antibodies that may reduce the effectiveness of standard replacement therapies. Decisions are expected in the U.S. in late 2024 and in the EU in early 2025.
Marstacimab has been given fast track and orphan drug designation in the U.S., as well as orphan drug status in the EU for treating hemophilia.
Therapy snapshot
Treatment name: | Marstacimab |
Administration: | Being tested in hemophilia as a subcutaneous injection |
Clinical testing: | In Phase 3 testing and now being considered for U.S., EU approval |
How does marstacimab work in hemophilia?
In hemophilia, certain proteins needed for the blood to clot — specifically clotting factor VIII (FVIII) in the case of hemophilia A and clotting factor IX (FIX) in hemophilia B — are either missing or dysfunctional. Lower than normal activity of these factors impairs blood clotting and causes patients to be more prone to excessive and prolonged bleeding, which can happen spontaneously or after a trauma or injury.
Marstacimab is an antibody-based treatment that’s designed to block the activity of a protein called tissue factor pathway inhibitor. This protein normally helps prevent the formation of blood clots. By blocking it, marstacimab should promote blood clotting and thereby help prevent bleeds in people with hemophilia. The therapy is expected to work similarly in people with either type of hemophilia, irrespective of inhibitor status.
How will marstacimab be administered in hemophilia?
In a Phase 3 trial of people with hemophilia, marstacimab was administered by a subcutaneous injection via an auto-injector pen. It was given at a loading dose of 300 mg, followed by once-weekly 150 mg doses.
If approved, marstacimab would become the first treatment for either hemophilia A or B that’s given at a flat dose, and would be the first once-weekly subcutaneous injection therapy to become available for hemophilia B.
Marstacimab in hemophilia clinical trials
Marstacimab has been evaluated across a range of clinical studies involving hemophilia patients. The therapy was assessed in a Phase 3 clinical trial and is now under regulatory review in the U.S. and Europe.
Phase 1b/2 trial
A Phase 1b/2 clinical trial (NCT02974855) tested marstacimab in 26 male patients with hemophilia, including 23 with hemophilia A and three with hemophilia B. Seven of those with hemophilia A had inhibitors. Participants were given marstacimab at varying doses once weekly for three months.
Marstacimab was able to reduce bleeding rates in patients with and without inhibitors. The therapy was also found to be generally well tolerated. Four patients had serious side effects, which weren’t deemed to be related to treatment, and two left the study due to side effects.
BASIS Phase 3 trial
Pfizer’s applications for marstacimab’s approval for hemophilia patients without inhibitors were mainly based on data from an ongoing Phase 3 clinical trial called BASIS (NCT03938792). The study enrolled more than 100 male patients with severe hemophilia A or moderately severe to severe hemophilia B, ages 12-74, with or without inhibitors.
For the first six months, patients participated in an observational period where they received standard replacement therapies or bypassing agents to manage bleeds. After this, all received prophylactic treatment with marstacimab for about a year. They were initially given a 300 mg subcutaneous loading dose, followed by 150 mg doses once weekly. Marstacimab maintenance doses could potentially be increased to 300 mg once weekly during the study under certain conditions.
Results from 116 patients without inhibitors showed that patients had lower bleeding rates after switching to marstacimab compared with the observational period. Specifically, the patients who’d been on preventive replacement therapy saw a 35% reduction in bleeding rates, while bleed rates fell by 92% for those who’d been using on-demand replacement therapy. Statistical tests also showed marstacimab was at least non-inferior to replacement therapy at lowering bleed rates and improving patients’ quality of life.
At the time results from patients without inhibitors were announced in mid-2023, the part of the BASIS trial that’s testing marstacimab in patients with inhibitors was still recruiting participants. The study is expected to conclude in 2025.
Other ongoing trials
Participants who complete the BASIS trial can enter an open-label extension study (NCT05145127) to continue receiving marstacimab for up to seven years. Interim data from the extension study have suggested marstacimab’s effect on bleeding rates is consistent over time.
Available data from BASIS and its extension also suggested marstacimab has generally been well tolerated. No deaths or abnormal blood clotting incidents were reported. One patient had a severe side effect of swelling in the extremities that was deemed to be related to treatment.
Another ongoing Phase 3 trial called BASIS KIDS (NCT05611801) is testing marstacimab in children with hemophilia as young as a year old. The trial is open to children with severe hemophilia A or moderately severe to severe hemophilia B, with or without inhibitors, who have been on standard replacement therapy or bypassing agents for at least a year.
The trial aims to enroll about 100 participants, and recruitment is ongoing at sites around the world. All participants will receive weekly subcutaneous injections of marstacimab, with the aim of evaluating the its effect on bleeding rates after about one year. Results are expected in late 2028. A subset of children and adolescents who participate and complete BASIC KIDS — those ages 12-18 who will make up the study’s first age group — will be eligible to enroll in the long-term extension study, along with BASIS study participants.
Common side effects of marstacimab
The most common safety issues reported among hemophilia patients given marstacimab in clinical trials include:
- Injection site reactions, such as pain or swelling
- High blood pressure
- COVID-19
- Bleeding
- Liver disorders
- Allergies
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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