Marstacimab up for approval for hemophilia in US, Europe

FDA expected to decide in late 2024; EC decision due in 2025

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The once-weekly injection therapy marstacimab is being considered for approval in both the U.S. and Europe for people with hemophilia A and hemophilia B who don’t have inhibitors.

The U.S. Food and Drug Administration (FDA) is expected to decide on it in late 2024, while a decision from the European Commission is expected in early 2025, according to marstacimab’s developer Pfizer.

If it’s approved, it would become the first medication for types A or B that’s given at a flat dose, and it would be the first once-weekly treatment for hemophilia B administered as an injection under the skin, or subcutaneously.

“Marstacimab has demonstrated that it may be an efficacious treatment option with once-weekly, subcutaneous flat-dose administration via an auto-injector pen for appropriate patients, if approved,” said James Rusnak, MD, PhD, senior vice president and chief development officer for internal medicine and infectious diseases, and research and development at Pfizer, in a company press release. “This is critical as intravenous infusions are typically required for people living with these diseases today We look forward to progressing the review of this novel therapy with the FDA, EMA [European Medicines Agency], and global regulatory authorities to bring this important medicine to patients globally.”

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What does marstacimab do in hemophilia?

Hemophilia A and B are caused by mutations that disrupt the activity of blood clotting proteins: factor VIII in type A and factor IX in type B. Standard treatment involves replacement therapy, wherein a lab-made, working version of the faulty or missing clotting factor is delivered directly into a patient’s bloodstream.

Some patients develop antibodies against the delivered clotting factor, however. These antibodies are called inhibitors because they stop the therapies from working appropriately.

Marstacimab is an antibody that suppresses the activity of tissue factor pathway inhibitor, a protein that normally helps prevent blood clotting. Given as a preventive treatment once a week, marstacimab is expected to help prevent or reduce bleeds in hemophilia A and B patients, regardless of their inhibitor status.

Pfizer’s applications for the therapy’s approval for patients without inhibitors are based mainly on data from patients without such antibodies in an ongoing Phase 3 clinical trial called BASIS (NCT03938792).

The study enrolled 173 boys and men, ages 12-74, with severe hemophilia A or moderate to severe hemophilia B and with or without inhibitors. It was designed to test marstacimab against standard replacement therapy.

The participants were observed for six months while they received standard replacement therapies either as routine prophylaxis, or preventive, treatment or on demand to manage bleeds. Then, all were given a 300 mg loading dose of marstacimab followed by once-weekly 150 mg doses of it for about a year.

Results of Phase 3 study

A total of 116 patients without inhibitors completed the observation period with standard treatment and received at least one dose of marstacimab. Their median age was 30 (range, 13-66) and most identified as white (50.8%) or Asian (47.7%).

Full results from this group of patients were shared last week at the 65th annual meeting of the American Society of Hematology (ASH), in the oral presentation “Efficacy and Safety of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants with Severe Hemophilia without Inhibitors: Results from the Phase 3 Basis Trial.”

Marstacimab led to a 35.2% reduction in average bleeds a year among patients on prophylaxis in the observation period (7.85 to 5.08 bleeds). This reduction was even more pronounced among those given on-demand treatment in the observation period — a 91.6% drop in yearly bleeds.

Marstacimab was at least not inferior to standard prophylaxis and on-demand treatment at reducing bleeds, including spontaneous or joint bleeds, statistical tests showed. It was also not inferior to standard prophylaxis at improving health-related quality of life.

The effects of marstacimab on bleeding rates were generally consistent across people with hemophilia A or B, and across different age groups.

After a year of marstacimab treatment, BASIS participants had the option to enroll in an open-label extension study (NCT05145127) where they’re all receiving the experimental therapy for up to seven years.

Available data from 87 patients treated for up to nearly 1.5 years in the extension indicated marstacimab’s effects on bleeding rates remain consistent with longer treatment.

“Recognizing the uncertainty that living with hemophilia can present for patients, the results from the BASIS trial are particularly encouraging as reductions in [annualized bleeding rates] were seen in the 12-month treatment period and then retained in long-term follow-up,” Davide Matino, MD, who presented the data at ASH, said in a separate Pfizer press release.

“Marstacimab has shown the potential to address the diverse needs of appropriate patients with hemophilia A or B without inhibitors with weekly subcutaneous administration in a flat dose that is not weight-based, and with low monitoring requirements,” said Matino, an assistant professor of medicine at McMaster University in Canada, one of the trial’s sites.

The therapy was generally well tolerated in the BASIS trial. One patient had serious treatment-related swelling of the extremities and another left the trial due to a serious side effect that was deemed unrelated to marstacimab. No deaths occurred.

Most common safety-related issues in BASIS and the extension study included COVID-19, bleeding, liver disorders, allergies, high blood pressure, and injection site reactions.

“Based on these results and if approved, we believe marstacimab could offer a subcutaneous option with a compelling combination of efficacy and safety that may significantly reduce the risk of bleeding,” Rusnak said.

Data from the inhibitor patient group in BASIS are expected late next year.