An experimental Pfizer hemophilia drug that takes a new approach to treating the blood clotting disorder has met the main goal of a pivotal study, setting the stage for regulatory submissions planned for later this year.

The drug, marstacimab, is being evaluated in hemophilia A as well as the less common hemophilia B. Standard of care for both forms of hemophilia includes clotting factor treatments, infusions of the clotting proteins that patients lack. But these therapies don’t last long in the body, so they must be administered every two-to-three days. Pfizer’s once-weekly injectable drug is a non-factor therapy.

The results reported Tuesday are from an open-label Phase 3 study enrolling patients with hemophilia with or without inhibitors, the antibodies that patients can develop to factor treatments. Those study participants were first observed for six months on their current treatment regimen, including intravenous infusions of factor treatments for preventing bleeds as well as for on-demand treatment of bleeds. Following that six-month lead-in period, participants were then treated with marstacimab for 12 months.

Pfizer reported that in patients who received on-demand factor replacement therapy in the initial part of the study, marstacimab led to a 92% reduction in bleeds. In those who had received prophylactic factor therapies, the Pfizer drug led to a 35% reduction in annualized bleeding rates. Pfizer said its drug was well tolerated by patients. No deaths were reported in the study, nor were there any reports of blood clots or abnormal activation of procoagulant pathways.

Hemophilia A patients already have a non-factor drug option—Hemlibra. That blockbuster Roche drug is an antibody designed to mimic the function of a clotting protein called factor VIII. Its FDA approval covers the prevention of bleeding episodes. Marstacimab is also an antibody, but the Pfizer drug works in a different way. It’s designed to block tissue factor pathway inhibitor (TFPI), an anticoagulant protein in the body that inhibits the start of the blood clotting process. According to Pfizer, by targeting the Kunitz-2 domain of this protein, marstacimab may help reestablish the balance between bleeding and blood clot formation.

Novo Nordisk is in the anti-TFPI chase with its antibody, concizumab, designed to treat both hemophilia A and B. Last month, the FDA rejected an application seeking approval, asking for more information about the monitoring and dosing of patients, the company disclosed in first quarter 2023 financial report. The FDA also asked for additional information about the drug’s manufacturing process. Concizumab is already approved in Canada for treating hemophilia B with inhibitors and is currently under regulatory review there for hemophilia A with inhibitors.

Pfizer said analysis of the full Phase 3 data for marstacimab is ongoing and results will be presented at an upcoming scientific conference. In the meantime, the company plans to discuss the data with regulators, followed by regulatory submissions it expects to file in coming months.

“These results support the potential for marstacimab to become the first once-weekly non-factor treatment for people with hemophilia B and a treatment option that helps address the diverse needs of patients with hemophilia A or B without inhibitors,” Chris Boshoff, chief development officer, oncology and rare disease, Pfizer global product development, said in a prepared statement. “These needs include preventing excessive or potentially life-threatening bleeds, while at the same time reducing the burden of treatment with once-weekly, subcutaneous administration.”

The Pfizer data for marstacimab come as competition in the hemophilia space heats up. Sanofi earlier this year won FDA approval for Altuviiio, a once-weekly treatment for hemophilia A. Gene therapies offer the potential for a one-time treatment of the inherited disorder. Pfizer has reached late-stage clinical development with gene therapies for hemophilia A and B. CSL Behring received FDA approval last fall for Hemgenix, a hemophilia B gene therapy. A hemophilia A gene therapy from BioMarin Pharmaceutical, Roctavian, is under FDA review and expected to receive a regulatory decision by the end of June.

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