Marstacimab reduces ABR in patients 12 years and up with hemophilia A or B with inhibitors | Image Credit: © lexiconimages - © lexiconimages
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On June 26, 2025, Pfizer announced positive topline results from the phase 3 BASIS study (NCT03938792) evaluating marstacimab (Hympavzi) in patients aged 12 years and older with hemophilia A or B with inhibitors. The once-weekly subcutaneous therapy showed statistically significant and clinically meaningful reductions in bleeding compared to on-demand therapy, according a press release from the company.¹

These new results follow the FDA approval of marstacimab on October 11, 2024, for the treatment of hemophilia A without factor VIII inhibitors and hemophilia B without factor IX inhibitors.²

BASIS trial: inhibitor cohort results

In the phase 3 BASIS trial, 48 participants with severe hemophilia A or B with inhibitors received marstacimab over a 12-month active treatment period following a 6-month on-demand observational period using bypassing agents. Patients treated with marstacimab had a 93% reduction in annualized bleeding rate (ABR) compared to on-demand therapy over 12 months (ABR 1.39 vs 19.78; P < 0.0001).¹

Superiority was also demonstrated across all bleeding-related secondary endpoints, including spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds. The treatment regimen involved a 300 mg subcutaneous loading dose followed by 150 mg weekly, with the potential for dose escalation to 300 mg.¹

No deaths or thromboembolic events were reported, and the treatment was generally well tolerated, consistent with the non-inhibitor cohort of the same study.

“Patients with inhibitors tend to face frequent complications, and navigating the treatment landscape can introduce complexities and increase disease burden,” said Davide Matino, MD, MSc, of McMaster University and BASIS principal investigator in a statement. “The strong bleed reduction with HYMPAVZI compared to on-demand treatment in the Phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options.”¹

Mechanism and regulatory background

Marstacimab is the first anti-tissue factor pathway inhibitor (TFPI) therapy approved in the United States and Europe for hemophilia A or B. It offers an alternative to factor replacement by targeting the Kunitz 2 domain of TFPI, aiming to rebalance coagulation rather than replace deficient clotting factors.^1,2

The FDA approval earlier this year was based on results from the BASIS trial’s non-inhibitor cohort. In that population, marstacimab reduced the estimated ABR from 38 to 3.2 when patients transitioned from on-demand factor therapy to once-weekly marstacimab.²

Common adverse events across studies included injection site reactions, pruritus, and headache. The product carries warnings about blood clots, hypersensitivity reactions, and potential embryofetal toxicity.

“The approval of [marstacimab-hncq] is a meaningful advancement for people living with hemophilia A or B without inhibitors for bleed prevention, with a generally manageable safety profile and a straightforward once-weekly subcutaneous administration,” said Suchitra S. Acharya, MD, at the time of FDA approval. "[Marstacimab-hncq] aims to reduce the current treatment burden by meeting an important need for these patients, including many who have required frequent, time-consuming intravenous treatment infusion regimens," said Acharya.²

Pfizer noted that the full phase 3 dataset from the inhibitor cohort of BASIS is ongoing, with additional data to be presented at "upcoming medical meetings." The company plans to discuss data with regulatory authorities, with the goal of "initiating regulatory filings for [marstacimab] for the treatment of patients living with hemophilia with inhibitors," according to the press release.¹

References:

1. Pfizer announces positive topline phase 3 results for Hympavzi in hemophilia A or B with inhibitors. Pfizer. Press release. June 26, 2025. Accessed June 26, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-3-results?cid=em_PfizerNewsroomAlert&ttype=em
2. Fitch J. FDA approves marstacimab-hncq to reduce bleeding in hemophilia A, B patients. Contemporary Pediatrics. October 11, 2024. Accessed June 26, 2025. https://www.contemporarypediatrics.com/view/fda-approves-marstacimab-hncq-to-reduce-bleeding-in-hemophilia-a-b-patients