First Patient Dosed in Phase 3 Trial Testing Marstacimab, Pfizer’s TFPI Therapy

The first participant was dosed with the investigational therapy marstacimab in a Phase 3 clinical trial — still recruiting eligible patients across the globe — in adolescents and adults with severe hemophilia A or B.

Pfizer‘s marstacimab (PF‐06741086) is a human antibody that blocks a specific domain in an anticoagulant protein called tissue factor pathway inhibitor (TFPI). The new treatment is intended to prevent or reduce the frequency of bleeding episodes in people with these two types of severe hemophilia.

TFPI inhibition offers a potential alternative approach to standard replacement therapy, which supplies the clotting factors that are missing or defective in people with hemophilia A and B. Specifically, replacement therapy provides factor VIII (FVIII) to people with hemophilia A and factor IX, or FIX, to those with hemophilia B.

“Targeting TFPI provides a novel approach to improve blood coagulation,” Brenda Cooperstone, chief development officer of rare disease at Pfizer Global Product Development, said in a press release.

“Marstacimab may have the potential to offer improved bleed control via subcutaneous [under-the-skin] injection and potentially eliminate the need for prophylactic factor replacement, providing an enhanced treatment option compared to factor replacement therapy,” Cooperstone said.

The Phase 3 trial, called BASIS (NCT03938792), is an international study taking place at multiple clinical sites across 17 countries. In the U.S., the trial is enrolling at Arkansas Children’s Hospital, with two more sites yet to open in Florida and New York. Sites in Bulgaria, Hong Kong, India, Japan, Korea, Russia, and Turkey also are enrolling, with others also still to open.  More information and contacts can be found here.

BASIS intends to recruit approximately 145 male adolescents and adults, ages 12 to 74, with severe hemophilia A or B — defined as FVIII or FIX activity under 1%, with or without inhibitors (neutralizing antibodies). About 20% of participants will be adolescents. More details on enrollment criteria are available on the trial site.

The trial will compare the effectiveness of marstacimab to standard replacement therapy or bypass therapy, which are treatments that “bypass” the need for clotting factor treatment.

After a six-month observation phase on their current hemophilia regimen (replacement therapy or bypass therapy), the patients will be assigned to treatment with marstacimab. Participants will receive a 300 mg starting dose, followed by a 150 mg dose once weekly. A higher weekly dose of 300 mg will be given to participants meeting dose increase criteria.

The study’s primary goal will be to assess the impact of treatment with marstacimab on the annualized bleeding rate (ABR) — the number of bleeds per year — after one year of treatment. Other assessments will include incidence and severity of thrombotic events (blood clots that can obstruct blood vessels) and of side effects, the formation of anti-treatment antibodies, and the incidence of joint, spontaneous and total bleeds.

Adding to the positive results found in laboratory tests, a completed Phase 2 clinical trial (NCT02974855) showed that marstacimab was able to reduce ABR by more than 75% in all participants.

Also, in a long-term extension study (NCT03363321), marstacimab showed sustained efficacy for up to one year and led to no thrombotic events or serious adverse events using doses not inferior to those planned for BASIS.

The therapy has been granted fast track and orphan drug designations by the U.S. Food and Drug Administration and the European Medicines Agency.