Novel Monoclonal Antibody Reduces Bleeds in Hemophilia A and B

Derick Alison
Derick Alison
6 Min Read

SAN DIEGO — The investigational monoclonal antibody marstacimab reduced the rate of treated bleeds in patients with hemophilia A or B without inhibitors to factor VIII or factor IX, the phase III BASIS trial showed.

The annualized bleeding rate (ABR) for treated bleeds was reduced by 91.6% with marstacimab versus on-demand therapy with factor VIII or factor IX concentrates, and by 35.2% compared with routine prophylactic care, reported Davide Matino, MD, MSc, of McMaster University in Hamilton, Ontario.

“Marstacimab was effective and safe for reducing bleeds in participants with severe hemophilia A or moderate to severe hemophilia B without inhibitors at 12 months in the phase III study, and up to an additional 16 months in the long-term extension study,” Matino said during a session at the American Society of Hematology annual meeting.

Pfizer, the drug’s developer, announced Monday that based on efficacy and safety data from the BASIS trial, the FDA has accepted the biologics license application for marstacimab, with a decision date set for the fourth quarter of 2024.

According to the company, if approved, marstacimab is expected to be the first once-weekly subcutaneous treatment for people living with hemophilia B, and the first treatment administered as a flat dose for people living with hemophilia A or B.

Marstacimab is targeted to the tissue factor pathway inhibitor protein to improve hemostasis via the extrinsic pathway of blood coagulation. Previous phase I/II studies demonstrated the efficacy and safety of long-term administration of marstacimab up to 450 mg weekly for reducing bleeding episodes in adults with severe hemophilia A or hemophilia B, with or without inhibitors, compared with on-demand therapy.

In the BASIS trial, 128 participants (108 adults and 20 adolescents) with hemophilia A or B entered a 6-month observational phase following screening and were categorized according to factor replacement treatment — either an on-demand (37 patients) or routine prophylaxis (91 patients) intravenous regimen of factor VIII or factor IX administered as part of usual care.

Of these patients, 116 completed the observational period (33 on-demand and 83 routine prophylaxis) and crossed over to a 12-month active treatment period, receiving a single subcutaneous loading dose of 300 mg followed by once-weekly 150-mg marstacimab.

Among the patients who received treatment on-demand, the ABR for treated bleeds fell from a mean of 38 during the observational period to 3.2 after treatment with marstacimab, representing a 91.6% reduction in mean ABR during the active treatment period (P<0.0001). Ten of 33 participants had no treated bleeds with marstacimab.

Following the 12-month active treatment period, patients could continue to receive marstacimab in a long-term extension study, which showed that efficacy was maintained (ABR 0f 3.9) for up to an additional 16 months.

Among the patients who received routine prophylaxis as usual care, the ABR fell from a mean of 7.9 during the observational period to 5.1 after treatment with marstacimab, translating into a 35.2% reduction in mean ABR during the active treatment period, demonstrating non-inferiority and superiority (P=0.0376). About a third of patients did not have any treated bleeds with marstacimab. Efficacy was also maintained during the long-term extension in this group, with an ABR of 2.3.

Matino reported that the efficacy of marstacimab was generally consistent across all subgroups, including patients with hemophilia A and B, as well as in adolescents and adults.

Marstacimab also showed superiority compared with previous on-demand therapy for joint bleeds, spontaneous bleeds, target joint bleeds, and total bleeds (all P<0.0001), while marstacimab was shown to be non-inferior to routine prophylaxis with factor concentrates across these bleed categories.

There were also non-significant improvements in health-related quality-of-life parameters with marstacimab compared with on-demand therapy, and non-inferiority versus routine prophylaxis therapy.

Most adverse events were mild to moderate in severity, Matino reported, and no embolic or thrombotic events were observed with marstacimab in either the main or extension phase of the study.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.


The study was funded by Pfizer.

Matino reported relationships with Bayer, Pfizer, Novo Nordisk, Sanofi, Sobi, Spark, Octapharma, and Roche.

Primary Source

American Society of Hematology

Source Reference: Matino D, et al “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” ASH 2023; Abstract 285.

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