Marstacimab has demonstrated significant safety and efficacy for patients with hemophilia A and B in the phase 3 BASIS trial, recently approved by the US Food and Drug Administration (FDA) for prophylactic treatment. This monoclonal antibody targets tissue factor pathway inhibitor (TFPI), enhancing thrombin generation and clot formation independent of factor VIII (FVIII) and factor IX (FIX).
The efficacy of marstacimab was supported by findings from a previous phase 1b/2 study and a long-term phase 2 follow-up, which established its safety profile and pharmacological properties in adults with severe hemophilia A or B, regardless of the presence of inhibitors. Dr. Davide Matino from McMaster University and colleagues stated, “We present efficacy and safety results from the pivotal phase 3 marstacimab trial.”
Details of the BASIS Trial
The BASIS trial is an open-label, one-way crossover, multicenter study conducted at 52 centers across 9 countries. It enrolled male patients aged 12 to <75 years> with severe hemophilia A (FVIII levels of ≤1%) or moderately severe to severe hemophilia B (FIX levels of ≤2%). Participants were grouped into cohorts based on the presence of inhibitors, with this report focusing on those without inhibitors.
To qualify for the trial, patients were required to have a body weight of at least 35 kg and no history of inhibitors against FVIII or FIX. Those receiving routine prophylaxis (RP) prior to enrollment had to demonstrate at least 80% adherence to their prescribed regimen during the six months leading up to the study.
During the 12-month active treatment phase, patients initially received a loading dose of 300 mg of subcutaneous marstacimab, administered as two injections of 150 mg each. This was followed by weekly injections of 150 mg. Local investigators could adjust the dosage to 300 mg after 180 days if patients experienced breakthrough bleeding.
Key Findings and Outcomes
The primary efficacy endpoint was the annualized bleeding rate (ABR) for treated bleeding events with marstacimab compared to previous on-demand (OD) or routine prophylaxis (RP) therapies. Secondary endpoints included ABR for specific types of bleeds, such as joint and spontaneous bleeds, as well as patient-reported health-related quality of life (HRQoL).
Among the 128 patients enrolled in the observational phase, 116 patients received marstacimab during the active treatment period. The OD group, consisting of 33 patients, experienced a mean ABR reduction from 39.86 in the observational phase to 3.2 in the active treatment phase. This result underscores the superiority of marstacimab, with an estimated ABR ratio of 0.08 (95% CI, 0.057 to 0.113; P <0.0001). In the RP group of 83 patients, the mean ABR decreased from 7.9 to 5.09, demonstrating both noninferiority and superiority of marstacimab (estimated ABR difference, -2.81; 95% CI, -5.42 to -0.2; P = 0.0349). Notably, there were no deaths or thromboembolic events reported during the trial, indicating that marstacimab was safe and well-tolerated, with no unexpected side effects.
Despite the promising findings, the investigators acknowledged some limitations, including the relatively small sample size which restricted the analysis of thrombotic events. “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 six months of the active treatment phase,” Matino and colleagues noted.
The ongoing open-label extension study of marstacimab will further investigate its long-term efficacy and safety outcomes, potentially providing more comprehensive insights into its role in treating hemophilia A and B.
