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Marstacimab, a monoclonal antibody recently approved by the US Food and Drug Administration (FDA) for prophylactic treatment of patients with hemophilia A or B, has indicated its safety and efficacy in the phase 3 BASIS trial.¹

Marstacimab targets TFPI, alleviating inhibition of activated FX- and FVII-tissue factor complex and increasing thrombin generation and clot formation independent of FVIII and FIX. A prior phase 1b/2 study, accompanied by a long-term phase 2 follow-up, provided the evidence for marstacimab’s safety, efficacy, and dose-level pharmacokinetics and pharmacodynamics in adults with severe hemophilia A or B, with or without inhibitors.¹

“A phase 1b/2 study and its long-term phase 2 follow-up provided evidence for the safety, efficacy, and dose-level pharmacokinetics and pharmacodynamics of marstacimab in adults with severe hemophilia A or B, with or without inhibitors,” Davide Matino, MD, thrombosis and atherosclerosis research institute, McMaster University, and colleagues wrote. “We present efficacy and safety results from the pivotal phase 3 marstacimab trial.”¹

The BASIS trial is an open-label, 1-way crossover, multicenter phase 3 trial. Marstacimab was administered over a 12-month active treatment phase and at 52 centers across 9 countries. Patients were enrolled in 2 cohorts based on the presence of inhibitors – this particular release includes only the noninhibitor cohort.¹

To be included, patients were required to be male, aged 12-<75 years, with severe hemophilia A (FVIII levels of ≤1%) or moderately severe to severe hemophilia B (FIX levels of ≤2%), as well as a body weight of ≥35 kg at screening. The noninhibitor cohort exhibited no history of inhibitors against FVIII or FIX and were receiving either on-demand (OD) or routine prophylaxis (RP) before enrollment. Those receiving RP in the observational phase (OP) were required to have demonstrated ≥80% adherence with scheduled prophylaxis regimen during 6 months before enrollment.¹

Investigators grouped patients according to treatment received during the 6-month OP, which then progressed into a 12-month study period during which patients received a single loading dose of 300 mg subcutaneous marstacimab, administered as 2 150-mg injections. This was followed by once-weekly 150 mg injections in prefilled syringes. Dose escalation to 300 mg was allowed based on the local investigator’s discretion after day 180 for patients who met protocol-specified criteria based on breakthrough bleeding.¹

The primary efficacy endpoint was annualized bleeding rate (ABR) for treated bleeding events with marstacimab treatment versus previous OD or RP therapy during the OP. Secondary endpoints included ABR for specific bleed types, such as joint bleeds, spontaneous bleeds, and total bleeding evens, as well as patient-reported health-related quality of life (HRQoL).¹

Among the 128 patients included in the OP, 116 received marstacimab in the ATP. The OD group (n = 33) saw mean ABR decrease from 39.86 (95% CI, 33.05 to 48.07) in the OP to 3.2 (95% CI, 2.1-4.88) in the ATP, highlighting the superiority of marstacimab (estimated ABR ratio, 0.08; 95% CI, 0.057 to 0.113; P <.0001). In the RP group (n = 83), mean ABR decreased from 7.9 (95% CI, 5.14 to 10.66) in the OP to 5.09 (95% CI, 3.4 to 6.78) in the ATP, showing the noninferiority and superiority of marstacimab (estimated ABR difference, -2.81; 95% CI, -5.42 to -0.2; P = .0349). There were no deaths or thromboembolic events during the trial. Marstacimab was safe and well-tolerated with no unanticipated side effects.¹

Despite these clear efficacy results, investigators also highlighted a handful of limitations, which may have influenced the data. Among these was the study’s relatively limited sample size, preventing the analysis and characterization of thrombotic events.¹

“A general trend in the lowering of ABR for treated bleeds over time was observed in both OD and RP groups during the first and second 6 months of the ATP,” Matino and colleagues wrote. “Similar time-dependent improvements have also been observed in a pooled analysis of emicizumab phase 3 studies. However, the marstacimab open-label extension study will further explore long-term efficacy and safety outcomes.”¹

References

1. Matino D, Palladino A, Taylor CT, et al. Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial. Blood. 2025;146(14):1654-1663. doi:10.1182/blood.2024027468