Pfizer Inc. (NYSE: PFE)today announced that the European Commission (EC) has granted marketing authorization to expand the approved indication for HYMPAVZI® (marstacimab) to include patients 12 years of age and older weighing at least 35 kg with hemophilia A (congenital factor VIII [FVIII] deficiency) with FVIII inhibitors or hemophilia B (congenital factor IX [FIX] deficiency) with FIX inhibitors.
HYMPAVZI offers a combination of superior bleed protection compared to on-demand (OD) treatment that is well-tolerated with a straightforward, once-weekly subcutaneous injection administration that does not require routine treatment-related lab monitoring for this difficult-to-treat inhibitor patient population 12 years of age and older.
Inhibitors limit treatment options for people living with hemophilia and are associated with an increased risk of uncontrolled bleeding.1 These inhibitory antibodies neutralize factor replacement therapies and render them ineffective.1,2 Of the more than 800,000 people in the world living with hemophilia A or hemophilia B, approximately 20% of those with hemophilia A and 3% of those with hemophilia B are unable to continue taking factor replacement therapies because they developed inhibitors to FVIII and FIX, respectively, and these therapies no longer prevent or stop bleeding episodes, particularly in individuals who are refractory to immune tolerance induction therapy.1,2,3
"Inhibitors present a substantial challenge for people living with hemophilia as they neutralize traditional factor replacement therapies, in turn limiting treatment options and leaving patients vulnerable to uncontrolled bleeding episodes," said Dr. Laurent Frenzel, Head of the Hemophilia Treatment and Research Center at the Necker-Enfants malades Hospital (Paris Cité). "The approval of HYMPAVZI offers adults and adolescents in the EU a once-weekly subcutaneous option that has demonstrated the ability to reduce bleeding episodes and maintain bleed reduction based on observation to date in a long-term extension study."
"For people living with hemophilia with inhibitors, recurring bleeding episodes can lead to damaged joints and introduce real limitations and disruptions to everyday life," said Alexandre de Germay, Chief International Commercial Officer and Executive Vice President, Pfizer. "This approval brings a once-weekly medicine to the EU that meets a critical need for patients who face a treatment journey that can be complex and challenging with limited options available today, representing the latest step in Pfizer's more than 40-year commitment to advancing care for people living with hemophilia. We look forward to working with regulators globally to continue bringing HYMPAVZI to those who can benefit from it."
This indication extension is based on results from the Phase 3 BASIS trial (NCT03938792extlink label) that evaluated the efficacy and safety of HYMPAVZI in adults and adolescents 12 years and older with severe hemophilia A or moderately severe to severe hemophilia B with inhibitors:
- In the active treatment period of the study, HYMPAVZI treatment resulted in a statistically significant and clinically meaningful 93% reduction in the mean treated annualized bleeding rate (ABR) (1.39 [95% CI: 0.85-2.29] vs.19.78 [95% CI: 16.12-24.27]; p<0.0001), demonstrating superiority over OD therapy.
- Superiority (p≤0.0001) of HYMPAVZI was also demonstrated across all measured bleeding-related secondary endpoints - spontaneous bleeds, joint bleeds, target joint bleeds, and total treated and untreated bleeds.
- In an interim analysis of the open-label extension trial, where patients were treated with HYMPAVZI for up to an additional 41 months (a total of 53 months of treatment with HYMPAVZI), the mean (1.19 [95% CI: 0.72-1.95]) and median (0.00 [95% CI: 0.00-1.18]) treated ABRs remained low.
- The safety profile for HYMPAVZI was consistent with Phase 1/2 results, and the most frequently reported adverse events in the study were injection site reactions, headache, pruritus, hypertension, and rash. The most serious adverse event reported from the clinical studies with HYMPAVZI was thrombosis.
This marketing authorization is valid in all 27 EU member states, as well as in Iceland, Liechtenstein, and Norway. Separately, the U.S. Food and Drug Administration (FDA) accepted and granted Priority Review for the supplemental Biologics License Application (sBLA) for HYMPAVZI to expand its approved indication to include the treatment of hemophilia A or B patients 6 years and older with inhibitors, and pediatric patients (ages 6 to 11) with hemophilia A or B without inhibitors earlier this year. In the U.S., HYMPAVZI is currently approved for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A (congenital FVIII deficiency) without factor VIII inhibitors or hemophilia B (congenital FIX deficiency) without factor IX inhibitors. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date in the second quarter of 2026.
About HYMPAVZI
Discovered by Pfizer scientists, HYMPAVZI has a unique mechanism of action that is differentiated from FVIII and FIX replacement treatments. Instead of replacing missing or insufficient clotting factors, HYMPAVZI is intentionally designed to target tissue factor pathway inhibitor (TFPI), one of the body's natural mechanisms that inhibits the initiation of blood clotting. By targeting the Kunitz 2 domain of TFPI, HYMPAVZI may help re-establish balance between bleeding and blood clot formation with the goal of offering a combination of bleed protection and straightforward administration.
HYMPAVZI is a hemophilia treatment that has received regulatory approvals in more than 40 countries for eligible patients living with hemophilia A without factor VIII inhibitors, or hemophilia B without factor IX inhibitors. HYMPAVZI was the first anti-TFPI approved in the U.S. and EU for the treatment of hemophilia A or B and the first hemophilia medicine approved in the U.S. and EU to be administered via a pre-filled auto-injector pen. For eligible people living with hemophilia B, it is the first once-weekly subcutaneous prophylactic treatment. HYMPAVZI is a subcutaneous treatment option with a once-weekly dosing schedule and minimal preparation required for each individual administration.
Pfizer is also conducting BASIS KIDS, an open-label study investigating the safety and efficacy of HYMPAVZI in children <18 years of age with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors. Pfizer is continuing to evaluate the long-term safety and efficacy of HYMPAVZI in hemophilia patients with or without inhibitors who have successfully completed treatment in BASIS and BASIS KIDS in an ongoing open-label long-term extension study.
About the BASIS Clinical Trial
