Pfizer's HYMPAVZI gets European Commission Approval to Treat Severe Hemophilia A and B

Hympavzi is the first and only anti-tissue factor pathway inhibitor (anti-TFPI) approved in the European Union (EU) for the treatment of haemophilia A or B and the first haemophilia medicine approved in the EU to be administered via a pre-filled, auto-injector pen. Hympavzi offers a subcutaneous treatment option with a once-weekly dosing schedule and minimal preparation required for each individual administration.

“There is a considerable treatment burden associated with the standard-of-care options for haemophilia A and B, including time-consuming preparation and administration of infusions and injections potentially causing missed doses and an increased risk of bleeding,” said Dr. Laurent Frenzel, head of the Haemophilia Treatment and Research Center at the Necker-Enfants malades Hospital (Paris Cité). “Hympavzi is a significant advancement for eligible patients in that it may provide bleed prevention as well as once-weekly subcutaneous administration via a pre-filled pen.”

Haemophilia is a family of rare genetic blood diseases caused by a clotting factor deficiency (FVIII in haemophilia A, FIX in haemophilia B), impacting more than 800,000 people globally. Diagnosed in early childhood, haemophilia inhibits the blood’s ability to clot properly, increasing the risk of repeated bleeding inside the joints, which can lead to permanent joint damage. Despite significant progress in haemophilia treatment in recent years, many people living with the disease continue to experience bleeding episodes and manage their condition with frequent intravenous infusions that may need to be administered multiple times a week.

“Hympavzi offers a first-in-class treatment option for people living with haemophilia, a disease that often leads to recurring joint bleeds and can impact daily activities as simple as climbing stairs,” said Alexandre de Germay, chief international commercial officer and executive vice president, Pfizer. “This approval builds on Pfizer’s more than four-decade commitment to improve the standard of care in haemophilia, and we look forward to delivering this medicine that reduced bleeds as compared to factor prophylaxis and, importantly, requires limited preparation, meeting a key need for eligible patients.”

The marketing authorization is based on results from the pivotal phase 3 BASIS study (NCT03938792) that evaluated the efficacy and safety of marstacimab in adults and adolescents 12 years and older with severe haemophilia A or B without inhibitors. In the study, Hympavzi significantly reduced the annualized bleeding rate (ABR) for treated bleeds by 35% (ABR of 5.08 vs. 7.85, p-value 0.0376) during the 12-month active treatment period, demonstrating non-inferiority and superiority compared to routine prophylaxis (RP) with FVIII or FIX administered as part of usual care. The safety profile for Hympavzi was consistent with phase 1/2 results, and the most commonly reported adverse events in the study were injection site reactions, headache, pruritus, and hypertension.

This marketing authorization is valid in all 27 EU member states, as well as in Iceland, Liechtenstein, and Norway. The EC approval follows the regulatory approval of Hympavzi in the United States in October.

Pfizer’s more than 40-year effort to advance haemophilia treatment began with the introduction of recombinant treatments and has extended to the introduction of newer, advanced treatment modalities. In addition to recent regulatory approvals for Hympavzi, Pfizer reported positive results from a phase 3 programme investigating a gene therapy candidate in haemophilia A (giroctocogene fitelparvovec) in July and received regulatory approvals in Europe and the US for its haemophilia B gene therapy Beqvez (fidanacogene elaparvovec).

Discovered by Pfizer scientists, Hympavzi is a rebalancing agent that targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulation protein that functions to prevent the formation of blood clots and restore haemostasis.

Hympavzi is approved by the EC for the routine prophylaxis of bleeding episodes in patients aged 12 years and older weighing at least 35 kg with severe haemophilia A (congenital factor VIII [FVIII] deficiency, FVIII <1%) without FVIII inhibitors or severe haemophilia B (congenital factor IX [FIX] deficiency, FIX <1%) without FIX inhibitors.

The pivotal BASIS study is a global phase 3, open-label, multicenter study to evaluate the efficacy and safety of Hympavzi in adolescent and adult participants ages 12 to <75 years with severe haemophilia A (defined as FVIII <1%) or moderately severe to severe haemophilia B (defined as FIX activity =2%) with or without inhibitors.

The marketing authorization is based on data from 116 people living with severe haemophilia without inhibitors who were treated with marstacimab during a 12-month active treatment period (ATP) versus a RP regimen with FVIII or FIX, administered as part of usual care in a 6-month observational period. During the ATP, participants received prophylaxis (a 300 mg subcutaneous loading dose of marstacimab, followed by 150 mg subcutaneously once weekly) with potential for dose escalation to 300 mg once weekly in patients weighing = 50 kg when control of bleeding events is judged to be inadequate by the healthcare professional.

Also Read: Pfizer Gets CDSCO Panel Nod To Conduct Phase III CT of Rimegepant

Hympavzi reduced the ABR for treated bleeds by 35% after a 12-month ATP compared to RP treatment in patients with haemophilia A or B without inhibitors. In an interim analysis of the long-term extension study, a consistent reduction in mean ABR for treated bleeds of 2.79 (95% CI 1.90-4.09) was observed in up to an additional 16 months of follow-up (n=87). Hympavzi demonstrated non-inferiority across all bleeding-related secondary endpoints: spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds.

The safety profile for Hympavzi was consistent with phase 1/2 results and treatment was generally well-tolerated. The most commonly reported adverse events were injection site reactions, headache, pruritus, and hypertension.

The inhibitor cohort of the BASIS study is ongoing, with results expected in the third quarter of 2025. Pfizer is also conducting BASIS KIDS, an open-label study investigating the safety and efficacy of marstacimab in children 1 to <18 years of age with severe haemophilia A or moderately severe to severe haemophilia B with or without inhibitors.

Haemophilia is a family of rare genetic blood diseases caused by a clotting factor deficiency (FVIII in haemophilia A, FIX in haemophilia B), which prevents normal blood clotting. Haemophilia is diagnosed in early childhood and impacts more than 800,000 people worldwide. The inability of the blood to clot properly can increase the risk of painful bleeding inside the joints, which can cause joint scarring and damage. People living with haemophilia can suffer permanent joint damage following repeated bleeding episodes.

For decades, the most common treatment approach for haemophilia A and B has been factor replacement therapy, which replaces the missing clotting factors. Factor replacement therapies increase the amount of clotting factor in the body to levels that improve clotting, resulting in less bleeding.

The burden of intravenous infusions is believed to be a barrier to treatment adherence for some people living with haemophilia due in part to inconvenience, time constraints, and poor venous access. In a patient/physician/specialist nurse survey across six European countries, lack of time for treatment and convenience were among the leading reasons for not using the prescribed amount of clotting factor or skipping treatment administration.