Pfizer's hemophilia drug hits in phase 3, giving it a chance to leapfrog Novo Nordisk

Pfizer is looming large in Novo Nordisk’s rearview mirror. Weeks after seeing its rival for the hemophilia market stumble, Pfizer has reported phase 3 data that suggest its candidate is competitive and position it to file for approval in the coming months.

Novo Nordisk and Pfizer are both developing antibodies that target the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulation protein. Until recently, Novo Nordisk looked to have the upper hand, with phase 3 data on its anti-TFPI candidate concizumab in the bank and an FDA ruling on an approval filing imminent. But the FDA’s rejection of the approval request for concizumab has opened the door for Pfizer.

Data released Tuesday show Pfizer has a shot at seizing the opportunity. The results come from a phase 3 trial that tested Pfizer’s anti-TFPI antibody marstacimab in 116 patients with hemophilia A or B. Subjects, who didn’t have inhibitors to factor VIII or factor IX, received standard of care for six months and then switched to marstacimab for 12 months. 

Among patients who received on-demand factor replacement intravenous therapy in the lead-in period, switching to Pfizer’s investigational antibody reduced bleeds by 92%. Pfizer also showed the superiority of marstacimab compared to prophylaxis, with a 35% reduction in the annualized bleeding rate.

Novo Nordisk’s FDA rejection came in patients with inhibitors, a different population than that targeted in the Pfizer trial. The Danish drugmaker is targeting individuals without inhibitors, too, randomizing people to receive either no prophylaxis or concizumab prophylaxis. Pfizer expects to have data on its inhibitor cohort late next year at the earliest. 

Drug delivery was a factor in the recent concizumab complete response letter, with the FDA asking for additional information on the monitoring and dosing of patients to ensure the treatment is administered as intended. The FDA also asked for more information on the manufacturing process. Pfizer has an edge in terms of dosing, with marstacimab injected weekly and concizumab injected daily.

Novo Nordisk’s troubles give Pfizer a shot at overtaking its anti-TFPI rival. Both assets are differentiated from factor VIII and IX therapies. Rather than replacing clotting factors, the molecules try to reestablish a balance between bleeding and blood clot formation by acting on mechanisms that inhibit the initiation of blood clotting.