TOPLINE:

Marstacimab, a monoclonal antibody targeting tissue factor pathway inhibitor, reduced the mean annualized bleeding rate by 92% in on-demand patients and 35.5% in routine prophylaxis patients with hemophilia A or B without inhibitors. Weekly subcutaneous administration demonstrated superiority over both previous treatment approaches with no reported thromboembolic events.

METHODOLOGY:

• BASIS trial enrolled male patients aged 12-74 years with severe hemophilia A (factor VIII < 1%) or moderately severe-to-severe hemophilia B (factor IX < 2%) across 52 centers in 19 countries.
• Participants without inhibitors received either on-demand or routine prophylaxis therapy during a 6-month observational phase before receiving weekly subcutaneous 150 mg marstacimab during a 12-month active treatment phase.
• Eligible participants had body weight ≥ 35 kg at screening and no detectable or documented history of inhibitors against factor VIII or IX.
• Routine prophylaxis participants demonstrated ≥ 80% adherence with scheduled prophylaxis regimen during 6 months before enrollment.
• Primary endpoints included annualized bleeding rate for treated bleeds vs previous on-demand or routine prophylaxis during observational phase and safety.

TAKEAWAY:

• Of 128 participants enrolled in the observational phase, 116 received marstacimab in the active treatment phase.
• In the on-demand group (n = 33), the mean annualized bleeding rate decreased from 39.86 (95% CI, 33.05-48.07) to 3.20 (95% CI, 2.10-4.88), demonstrating superiority of marstacimab (estimated annualized bleeding rate ratio, 0.080; 95% CI, 0.057-0.113; P < .0001).
• In the routine prophylaxis group (n = 83), the mean annualized bleeding rate decreased from 7.90 (95% CI, 5.14-10.66) to 5.09 (95% CI, 3.40-6.78), demonstrating noninferiority and superiority of marstacimab (estimated annualized bleeding rate difference, -2.81; 95% CI, -5.42 to -0.20; P = .0349).
• No deaths or thromboembolic events were reported during the study period.

IN PRACTICE:

“Marstacimab was safe and well tolerated over 12 months, with no deaths or thromboembolic events. Safety, immunogenicity, and laboratory parameters were consistent with previous studies and contrast other investigational nonfactor treatments associated with thromboembolic complications,” the authors of the study wrote.

SOURCE:

This study was led by Davide Matino, Thrombosis and Atherosclerosis Research Institute and Department of Medicine, McMaster University, Hamilton, Ontario, Canada. It was published online in Blood.

LIMITATIONS:

This study had a limited sample size to fully characterize thrombotic events, with none reported ruling out > 2.55% of the true thromboembolic rate with one-sided 95% confidence. While the COVID-19 pandemic had potential to affect recruitment, treatment suspension, and health-related quality-of-life assessments, researchers reported minimal impact on study conduct.

DISCLOSURES:

This study was funded by Pfizer. Several authors were employees and stockholders of Pfizer at the time the study was conducted. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.