Pfizer recently provided new clinical trial updates for their investigational therapy marstacimab. The data was presented last month at the 2024 annual meeting of the European Hematology Association (EHA) in Madrid. Marstacimab is a laboratory-engineered monoclonal antibody developed to treat hemophilia A and B patients, with or without inhibitors.
Marstacimab targets an anticoagulant protein known as tissue factor pathway inhibitor (TFPI). It works by blocking and effectively preventing TFPI from performing the anticoagulant function that it naturally carries out in the human body. It is administered prophylactically via a once-weekly subcutaneous injection. This type of therapy allows treaters to forgo the need for regular prophylaxis with traditional, intravenously infused factor replacement.
These latest findings are an interim analysis of a long-term extension study of individuals participating in the non-inhibitor cohort of Pfizer’s BASIS clinical trial program. BASIS is evaluating annualized bleed rate (ABR) through one year of treatment with marstacimab in adolescent and adult participants between ages 12 to 75 years with severe hemophilia A or B, with or without inhibitors.
A total of 107 patients were included in this analysis. At the time of the reporting, 89 (83%) of the extension study participants were adults and 18 (17%) were adolescents. 83 (76%) patients had hemophilia A and 24 (22.4%) had hemophilia B. The mean age of participants was 29 years. Before switching to mastacimab, 32 patients had been treated on-demand with factor replacement therapy (FRT), while 75 received FRT as routine prophylaxis.
Hemophilia A and B patients who had previously received on-demand FRT showed substantial reductions in estimated ABR for treated bleeds, with a baseline of 38.0 compared to 3.2 after 12 months of therapy with Marstacimab. This reduction was sustained at an ABR of 3.7 after the mean additional 12.5 months in the extension study.
According to BASIS investigators, the corresponding estimated ABR rates in the routine prophylaxis group were 7.9 at baseline, 5.1 at the end of the trial, and 2.8 in the extension study analysis interim cutoff.
The release announcing these results also included commentary from hematologist Margaret Ragni, MD, MPH, professor of medicine and clinical and translational research in the Division of Hematology/Oncology at the University of Pittsburgh. She noted that marstacimab could represent an important addition in the prevention of bleeds in hemophilia patients. "[If marstacimab is approved], hemophilia B patients [will] have a drug that can be given subcutaneously weekly to rebalance hemostasis, reducing bleeds, just as hemophilia A patients have with emicizumab."
Dr. Ragni did add some caveats, noting that "neither [marstacimab nor emicizumab] treats bleeds. For that, standard factor replacement therapy or bypass for inhibitors, would be required."
She also explained that "a limitation with marstacimab is the lack of weight-dependent dosing. Furthermore, emicizumab can be given weekly, biweekly, or monthly, while that [variation in dosing] is not yet studied with marstacimab." Some participants had their dosage upped from 150 mg to 300 mg weekly if they experienced two or more spontaneous joint bleeds while receiving the 150 mg dose.
The long-term extension study will continue through a seven year follow up period to monitor safety and efficacy among participants.
Read the full abstract presented at the EHA meeting.
Source: Medscape (originally appearing on MDedge.com), June 28 , 2024
