According to the results of a phase 2 study presented at the International Society on Thrombosis and Haemostasis (ISTH) 2021 Virtual Congress, long-term treatment with the monoclonal antibody marstacimab was well tolerated and efficacious in patients with severe hemophilia.

Marstacimab promotes clotting activity by targeting an endogenous anticoagulant protein called tissue factor pathway inhibitor (TFPI). The open-label study ( Identifier: NCT03363321) evaluated long-term safety and efficacy of marstacimab in male patients with severe hemophilia A or B (factor VIII or factor IX ≤1%), with or without inhibitors. Patient who completed a previous short-term phase 1/2 dose escalation study of marstacimab ( Identifier: NCT02974855) could enroll in the study if aged ≥18 to <65 years, while de novo patients were eligible if aged ≥12 to <75 years and had ≥ 6 acute bleeding episodes in the 6 months prior to screening.

Patients received a 300-mg subcutaneous loading dose of marstacimab followed by either 150 mg or 300 mg once weekly for up to 1 year. The primary endpoints were safety outcomes, including treatment-emergent adverse events (TEAEs) and injection site reactions. Secondary and exploratory endpoints included efficacy, assessed as annualized bleeding rate (ABR), and frequency of antidrug neutralizing antibody production.

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The participants included 18 patients from the dose-escalation study and 2 de novo patients, with/without inhibitors. Patients were evenly divided between the 2 dose groups: 10 in the 150-mg dose and 10 in the 300-mg group.

The mean duration of marstacimab exposure was 318 days in the 150-mg dose group and 335 days in the 300-mg group. In total, 24 AEs (1 TEAE) occurred in 7 patients in the 150-mg cohort (70%) and 15 AEs (2 TEAE) occurred in 7 patients in the 300-mg cohort (70%).

TEAEs were injection-site reactions (n=2; 1 each 150-mg and 300-mg dose) and hematoma (n=1; 300-mg dose). Serious non-TEAEs (1 traumatic cerebral hemorrhage; 1 generalized tonic-clonic seizure) occurred in 1 patient. No patients discontinued treatment due to AEs, and no patients developed antidrug antibodies. No thrombotic events or serious TEAEs were reported.

Relative to the pretreatment period, the mean ABR decreased by 84.5% in the 150-mg dose group cohort and by 92.6% in the 300-mg dose group.

“Marstacimab treatment in this study was associated with decreased mean annualized bleeding rates compared with prestudy annualized bleeding rates, and maintenance of efficacy of the short-term parent study was observed in this cohort,” concluded study author Johnny Mahlangu, BSc, MBBCh, MMed, FCPath.

A phase 3 study ( Identifier: NCT03938792) is currently recruiting to evaluate the safety and efficacy of marstacimab (300 mg loading dose and 150 mg weekly) in patients with severe hemophilia A or B.

Disclosure: This research was supported by Pfizer Inc. Please see the original presentation for a full list of disclosures.


Mahlangu J, Lamas JL, Morales JC, et al. Long-term safety and efficacy of the anti-TFPI monoclonal antibody marstacimab in patients with severe haemophilia A or B: results from a phase 2 long-term treatment study.  Paper presented at: International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress; July 17-21, 2021; virtual. Abstract OC 32.4.