The phase 3 BASIS trial has confirmed the efficacy and safety of marstacimab, a recently FDA-approved monoclonal antibody for prophylactic treatment of hemophilia A and B patients. The pivotal study demonstrated significant reductions in bleeding rates across both on-demand and routine prophylaxis patient groups over a 12-month treatment period.
Mechanism and Trial Design
Marstacimab targets tissue factor pathway inhibitor (TFPI), alleviating inhibition of activated FX- and FVII-tissue factor complex and increasing thrombin generation and clot formation independent of FVIII and FIX. This mechanism allows the therapy to work effectively regardless of hemophilia type and inhibitor status.
The BASIS trial was conducted as an open-label, 1-way crossover, multicenter phase 3 study administered at 52 centers across 9 countries. The study included male patients aged 12 to less than 75 years with severe hemophilia A (FVIII levels ≤1%) or moderately severe to severe hemophilia B (FIX levels ≤2%), with body weight ≥35 kg at screening.
Treatment Protocol and Patient Population
Among 128 patients included in the observational phase, 116 received marstacimab in the active treatment phase. Patients were grouped according to their previous treatment: on-demand therapy (n=33) or routine prophylaxis (n=83). The treatment regimen consisted of a single loading dose of 300 mg subcutaneous marstacimab administered as two 150-mg injections, followed by once-weekly 150 mg injections in prefilled syringes.
Primary Efficacy Results
The primary efficacy endpoint measured annualized bleeding rate (ABR) for treated bleeding events with marstacimab treatment versus previous therapy. In the on-demand group, mean ABR decreased dramatically from 39.86 (95% CI, 33.05 to 48.07) during the observational phase to 3.2 (95% CI, 2.1-4.88) during the active treatment phase, demonstrating marstacimab's superiority with an estimated ABR ratio of 0.08 (95% CI, 0.057 to 0.113; P <.0001).
For patients previously receiving routine prophylaxis, mean ABR decreased from 7.9 (95% CI, 5.14 to 10.66) to 5.09 (95% CI, 3.4 to 6.78), showing both noninferiority and superiority of marstacimab with an estimated ABR difference of -2.81 (95% CI, -5.42 to -0.2; P = .0349).
Safety Profile
The trial demonstrated a favorable safety profile with no deaths or thromboembolic events reported during the study period. Marstacimab was safe and well-tolerated with no unanticipated side effects. Dose escalation to 300 mg was permitted based on investigator discretion after day 180 for patients meeting protocol-specified criteria for breakthrough bleeding.
Clinical Implications and Study Limitations
"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," noted lead investigator Davide Matino, MD, from McMaster University's thrombosis and atherosclerosis research institute, and colleagues. "Similar time-dependent improvements have also been observed in a pooled analysis of emicizumab phase 3 studies."
The investigators acknowledged the study's relatively limited sample size as a limitation that prevented comprehensive analysis and characterization of thrombotic events. The ongoing marstacimab open-label extension study will further explore long-term efficacy and safety outcomes.
"A strength of BASIS is the inclusion of participants with hemophilia A and B, with or without inhibitors, because marstacimab acts independently of FVIII and FIX and may represent an effective treatment regardless of hemophilia type and inhibitor status," the researchers emphasized.
