For a long time, the most common treatment approach for hemophilia A and B has been factor replacement therapy, which replaces missing clotting factors to facilitate proper blood coagulation.  Marstacimab is a novel, investigational treatment for hemophilia that is designed to restore hemostasis by inhibiting tissue factor pathway inhibitors (TFPI).

Pfizer currently has three Phase III programs investigating marstacimab or patients with severe hemophilia A and moderately severe to severe hemophilia B, with or without inhibitors, that include:

• BASIS study (NCT03938792): To demonstrate efficacy and safety in ages 12 to <75 years. Positive data from the completed non-inhibitor cohort have been presented. Inhibitor cohort is on-going.

• BASIS KIDS study (NCT05611801): To demonstrate efficacy and safety in ages 1 to 17 years.

• LTE (NCT05145127): Open-label, long-term extension (LTE) study for participants who complete the above pivotal studies.

In December 2023, Pfizer announced that the US FDA accepted the company’s Biologics License Application (BLA) for marstacimab for individuals living with hemophilia A or B without inhibitors to Factor VIII (FVIII) or Factor IX (FIX). The European marketing authorization application (MAA) for marstacimab also passed validation and is currently under review by the EMA. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date in the fourth quarter of 2024, and a decision from the European Commission is anticipated by the first quarter of 2025. 

Interim data for the LTE participants from the BASIS non-inhibitor cohort were presented at the EHA 2024 Congress. Participants entered the LTE on their marstacimab dose from the end of the pivotal study (150 mg or 300 mg SC weekly). Safety is the primary endpoint for this ongoing LTE study. 92.2% of non-inhibitor participants from the pivotal study have transitioned to LTE study, among which 83% were adults and 17% were adolescents. Overall compliance with marstacimab prophylaxis is high at 98.9 %.

The results showed mean estimates for total (treated + untreated) ABRs (annualized bleeding rates) for prior on demand and routine prophylaxis groups were 5.05 (3.43 – 7.41) and 3.17 (2.24 – 4.50), respectively. 

Marstacimab was found to be safe and well tolerated in patients with hemophilia in the pivotal and LTE studies. There were no reports of thromboembolic events occurrence. 

KOL Insights

“Recognizing the uncertainty that living with hemophilia can present for patients, the results from the BASIS trial are particularly encouraging as reductions in ABR were seen in the 12-month treatment period and then retained in long-term follow-up,” - MD, MSc, assistant professor of Medicine, United States

“Marstacimab has shown the potential to address the diverse needs of appropriate patients with hemophilia A or B without inhibitors with weekly subcutaneous administration in a flat dose that is not weight-based, and with low monitoring requirements,” added Matino.” - MD, MSc, assistant professor of Medicine, United States

Conclusion 

For more than five decades, the primary treatment for hemophilia A and B involved multiple weekly intravenous infusions. With the recent approval of BEQVEZ, a one-time gene therapy for adults with hemophilia B, by the US FDA and expected approval of marstacimab by year's end, Pfizer is stepping up their game in the hemophilia market.  If approved in the US and EU, marstacimab is expected to become the first once-weekly subcutaneous treatment for people living with hemophilia B and the first flat-dose treatment for hemophilia A or B. This Treatment offers a treatment option for those without reliable vascular access, enhancing convenience and potentially improving compliance.

Compared to current methods of treating hemophilia A or B, treatment with marstacimab has the potential to show a clinically relevant advantage and/or a significant improvement in patient care because, unlike factor replacement products, marstacimab is effective even in the presence of inhibitors.

Concizumab from Novo Nordisk, which is authorized in Canada (HAwI/HBwI), Australia (HAwI/HBwI), Switzerland (HAwI/HBwI) and Japan (HAwI/HBwI) under brand name ALHEMO, is anticipated to face competition from Pfizer. In April 2023, the US FDA requested further details from Novo Nordisk on the drug's manufacturing process as well as the company's patient monitoring and dosing mechanism to ensure that the therapy is given appropriately. The resubmission is expected during 2024. In February 2023, Novo Nordisk filed an application with the EMA. Despite the fact that both of these drugs are monoclonal antibodies, Pfizer's anti-TFPI drug has an advantage since concizumab is injected subcutaneously once daily, whereas marstacimab is administered once a week.

Results presented from the LTE study at the EHA 2024 demonstrated sustained or improved efficacy for treated and total ABR in adults and adolescents with HA or HB without inhibitors. These findings were consistent across participants who had received either on-demand or routine prophylaxis factor replacement therapy at baseline.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the following reports: 

• Hemophilia A Market Insight, Epidemiology And Market Forecast – 2034

• Hemophilia B Market Insight, Epidemiology And Market Forecast - 2034