Pfizer Inc. has revealed that the European Commission (EC) has authorized the market release of Hympavzi (marstacimab) for the routine prevention of bleeding episodes in individuals aged 12 and older, who weigh at least 35 kg, with severe hemophilia A (congenital factor VIII [FVIII] deficiency, FVIII <1%) without FVIII inhibitors, or severe hemophilia B (congenital factor IX [FIX] deficiency, FIX <1%) without FIX inhibitors. Hympavzi stands as the pioneering and exclusive anti-tissue factor pathway inhibitor (anti-TFPI) sanctioned within the European Union (EU) for managing hemophilia A or B and marks the first hemophilia treatment endorsed in the EU to be dispensed using a pre-filled, auto-injector pen. It unveils a subcutaneous treatment alternative with once-weekly dosing and minimal preparation for administration. "The treatment challenge associated with conventional care options for hemophilia A and B involves extensive preparation time and the risk of missed doses, leading to increased bleeding," noted Dr. Laurent Frenzel, head of the Hemophilia Treatment and Research Center at Necker-Enfants malades Hospital in Paris. "Hympavzi is a breakthrough for suitable patients, offering proactive prevention against bleeds and a user-friendly, once-a-week subcutaneous approach through a pre-filled pen." Hemophilia, a rare genetic blood disorder stemming from a deficiency of clotting factors (FVIII in hemophilia A, FIX in hemophilia B), affects over 800,000 people globally. Diagnosed during early childhood, hemophilia disrupts normal blood clotting, raising the risk of repeated internal joint bleedings which could cause lasting joint damage. Despite notable strides in hemophilia therapies, many continue to endure bleeding episodes and rely on frequent intravenous infusions, sometimes multiple times weekly. "Hympavzi provides an innovative treatment choice for those living with hemophilia—a condition leading to recurrent joint bleeds that can hamper everyday activities like ascending stairs," remarked Alexandre de Germay, Pfizer's chief international commercial officer. "This approval underscores Pfizer's decades-long dedication to elevating hemophilia care standards, and we aim to deliver this therapy that reduces bleeds compared to factor prophylaxis while requiring minimal preparation—a crucial requirement for eligible patients." The EC's approval is predicated on outcomes from the phase 3 BASIS study (NCT03938792), which assessed marstacimab's effectiveness and safety in adolescents and adults aged 12 and above with severe hemophilia A or B without inhibitors. The study revealed that Hympavzi significantly curtailed the annualized bleeding rate (ABR) for treated bleeds by 35% (ABR of 5.08 versus 7.85, with a p-value of 0.0376) over a 12-month active treatment timeframe, proving non-inferiority and superiority compared to FVIII or FIX routine prophylaxis (RP) administered as part of standard care. Hympavzi's safety profile was in line with phase 1/2 data, with the most frequent adverse events being injection site reactions, headache, pruritus, and hypertension. This marketing approval is valid in all 27 EU members along with Iceland, Liechtenstein, and Norway. Following U.S. regulatory success in October, the EU approval of Hympavzi exemplifies Pfizer's continual efforts to push the frontiers of hemophilia treatment, extending from recombinant therapies to groundbreaking treatment modalities. Hympavzi, discovered by Pfizer scientists, is a rebalancing agent targeting the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulant overseeing clot prevention and hemostasis restoration. Hympavzi received CE approval for routine bleeding episode prophylaxis in patients aged 12 and above, weighing at least 35 kg with severe FVIII (<1%) deficiency without inhibitors or severe FIX (FIX <1%) deficiency without inhibitors. The BASIS trial is a comprehensive phase 3, open-label, global, multicenter study examining Hympavzi efficacy and safety in adolescents and adults aged 12-<75 years with severe hemophilia A (FVIII <1%) or moderately severe to severe hemophilia B (FIX activity =2%) with or without inhibitors. Approval stems from data involving 116 individuals with severe hemophilia without inhibitors treated with marstacimab during a 12-month active treatment window versus RP with FVIII or FIX in a 6-month observational setting. During this period, subjects received prophylaxis (300 mg subcutaneous marstacimab loading dose, followed by 150 mg subcutaneously weekly) with the potential for dose elevation to 300 mg weekly in patients >= 50 kg if bleeding control was deemed insufficient by healthcare professionals.
Hympavzi cut the ABR for treated bleeds by 35% post 12-month ATP when compared to RP treatment in hemophilia A or B patients without inhibitors. Interim analysis of the long-term extension study showed a sustained mean ABR reduction of 2.79 (95% CI 1.90-4.09) over up to an extra 16 months follow-up (n=87). Hympavzi demonstrated non-inferiority across secondary endpoints linked to bleeding: spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds.
Hympavzi’s safety profile correlated with phase 1/2 results, showcasing general tolerance with frequent adverse events being injection site reactions, headache, pruritus, and hypertension.
The inhibitor group from the BASIS study is ongoing, with findings anticipated by the third quarter of 2025. Pfizer is also conducting BASIS KIDS, an open-label examination of marstacimab’s safety and efficacy in children aged 1 to <18 years with severe hemophilia A or B, with or without inhibitors. Hemophilia's roots lie in rare genetic blood disorders due to clotting factor deficiencies (FVIII in A, FIX in B), hampering normal blood clot formation. Early childhood brings diagnosis for over 800,000 people worldwide. Chronic joint bleeding can wreak havoc, resulting in joint damage. Frequent repetition morphs into permanent joint damage due to hemophilia. Historically, factor replacement therapy has defined hemophilia A and B treatment. These therapies heighten clotting factor availability, enhancing clot efficiency and reducing bleeding episodes. Intravenous infusion burdens likely impede treatment adherence due to inconvenience, time demands, and vein access challenges. A survey spanning six European nations revealed time constraints and ease as primary contributors to underutilizing prescribed clotting factor or missing treatment administration.