Research Summary

Marstacimab Reduces Bleeding Rates in Adolescent, Adult Men With Hemophilia A/B With Inhibitors

Edited by:
Ashton L. Stahl

Key Highlights

  • In the on-demand cohort, the mean treated annualized bleeding rate fell from 19.78 during observation to 1.39 with marstacimab.
  • More than half of participants in the on-demand group (54.2%) had no treated bleeds during active treatment.
  • Weekly subcutaneous marstacimab was associated with improved patient-reported quality of life measures.
  • No thromboembolic events were reported during the 12-month active treatment phase.

Weekly subcutaneous marstacimab significantly reduced bleeding rates in adolescent and adult men with hemophilia A or B with inhibitors in the phase 3 BASIS trial, according to findings published in Blood. Among participants previously managed with on-demand bypassing agents, marstacimab reduced the mean annualized bleeding rate (ABR) for treated bleeds from 19.78 (95% CI, 16.12-24.27) during the observational phase to 1.39 (95% CI, 0.85-2.29) during active treatment (ABR ratio, 0.07; 95% CI, 0.042-0.118; P < .0001). The investigators reported that marstacimab had an acceptable safety profile, with no unanticipated adverse effects in this inhibitor population.

BASIS was an open-label, single-arm, 1-way crossover phase 3 trial conducted at 52 centers across 19 countries. The study enrolled males aged 12 to <75 years with severe hemophilia A or with moderately severe to severe hemophilia B and inhibitors. Participants completed a roughly 6-month observational phase on prior therapy, including on-demand or routine prophylaxis with bypassing agents, followed by a 12-month active treatment phase with marstacimab. Treatment consisted of a 300-mg loading dose administered as 2 subcutaneous injections of 150 mg each, followed by 150 mg once weekly, with dose escalation to 300 mg permitted after day 180 for protocol-specified breakthrough bleeding. Primary endpoints were ABR for treated bleeds and safety.

Study Findings

Of 107 screened participants, 60 entered the observational phase, and 51 entered the active treatment phase and received marstacimab. In the on-demand group, 48 participants were included in the efficacy analysis. Median marstacimab treatment duration was 364 days, and adherence was 98.2%. In addition to the primary endpoint, key secondary bleeding endpoints also favored marstacimab. The mean ABR for treated joint bleeds declined from 15.2 to 1.1, spontaneous treated bleeds from 15.3 to 0.9, target joint treated bleeds from 6.4 to 0.8, and total bleeds from 27.3 to 4.4. The results were consistent by hemophilia type: the ABR ratio was 0.05 in hemophilia A and 0.13 in hemophilia B. Among participants in the on-demand group, 26 of 48 (54.2%) had no treated bleeds during active treatment, compared with 1 of 48 (2.1%) during observation. Patient-reported outcomes also improved, including the Haem-A-QoL Physical Health domain (median difference, –25.9; P < .0001), Haem-A-QoL total score (–13.5; P < .0001), and EQ-5D-5L index score (0.1043; P = .0377).

Clinical Implications

According to the study authors, these findings suggest that marstacimab may be a viable prophylactic treatment option for people with hemophilia A or B with inhibitors. The authors noted that the open-label crossover design, small sample size, and short follow-up limit direct comparisons with other prophylactic strategies and the interpretation of long-term safety.

Expert Commentary

“Together with findings from the noninhibitor cohort, these results suggest that marstacimab may help to address an unmet need for treatment options that can be used by people with hemophilia regardless of hemophilia type or inhibitor status,” the researchers concluded.

Reference

Matino D, Acharya SS, Taylor CT, et al. Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial. Blood. 2026;147(9):920-931. doi:10.1182/blood.2025031065