Pfizer Inc. (NYSE: PFE)today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for HYMPAVZI® (marstacimab-hncq) to include the treatment of patients with hemophilia A or B 12 years and older with inhibitors and pediatric patients (ages 6 to 11 years) with or without inhibitors. HYMPAVZI is now indicated in the U.S. for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and pediatric patients 6 years of age and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors, or hemophilia B (congenital factor IX deficiency) with or without factor IX inhibitors.
HYMPAVZI offers a combination of prophylactic bleed protection with a straightforward, once-weekly subcutaneous administration that does not require routine treatment-related lab monitoring.
"For children who have to deal with bleeding episodes from an early age and for people living with hemophilia who develop inhibitors, treatment options have been limited and are often burdensome," said Guy Young, M.D., Director, Hemostasis and Thrombosis Center at Children's Hospital, Los Angeles. "A treatment that can reduce bleeding with straightforward, once-weekly administration has the potential to fundamentally change how patients and caregivers approach this disease, offering control with a level of simplicity this community has long needed."
Hemophilia is typically diagnosed in early childhood and impacts more than 800,000 people worldwide.1 The inability of the blood to clot properly can increase the risk of painful bleeding, including inside the joints, which can cause joint scarring and damage.2,3 Children's joints have growing cartilage and bone, which makes them particularly susceptible to damage caused by repeated bleeding episodes.4
Inhibitors to factor replacement therapy limit treatment options for people living with hemophilia and are associated with an increased risk of uncontrolled bleeding.5 These inhibitory antibodies develop in approximately 20% of those with hemophilia A and 3% of those with hemophilia B.5 Many people living with inhibitors to FVIII and FIX are unable to continue taking factor replacement therapies as they no longer prevent or stop bleeding episodes, particularly in individuals who are refractory to immune tolerance induction therapy.1,5,6
"With this expanded approval, we believe HYMPAVZI can become a transformative option and meet a significant medical need for people living with hemophilia A or B with or without inhibitors ages 6 years and older. Particularly for children ages 6 to 11 with hemophilia B who will now, for the first time, have a subcutaneous non-factor treatment available," said Aamir Malik, Chief U.S. Commercial Officer and Executive Vice President, Pfizer. "This milestone represents the latest step in Pfizer's more than 40-year commitment to advancing care and quality of life for people living with hemophilia, which began with the introduction of recombinant therapies and has evolved with the introduction of this once-weekly subcutaneous treatment."
Results from the Phase 3 BASIS trial (NCT03938792extlink label) supported the approval of HYMPAVZI in adults and adolescents 12 years and older with hemophilia A or B with inhibitors. The results demonstrated the superiority of HYMPAVZI in improving key bleeding outcomes including significantly reducing mean treated annualized bleeding rate (ABR) by 93% compared to on-demand (OD) intravenous treatment with bypassing agents (1.4 [95% CI: 0.9-2.3] vs.19.8 [95% CI: 16.1-24.3]; p<0.0001).
Interim results from the Phase 3 BASIS KIDS trial (NCT05611801extlink label) supported the approval of HYMPAVZI in children ages 6 to 17 years with hemophilia A or B with or without inhibitors. Descriptive analyses, which summarize trends in the data, in patients who received HYMPAVZI demonstrated:
- In children ages 6 to 17 years old without inhibitors, a mean treated ABR of 1.8 (99% CI: 1.1-2.6) was observed in patients who received HYMPAVZI compared to a historical model-based mean ABR of treated bleeds of 3.6 (99% CI: 1.3-5.8) in patients who received routine prophylaxis
- In children 6 to 17 years old with inhibitors, a mean treated ABR of 1.4 (99% CI: 0.5-4.5) was observed in patients who received HYMPAVZI compared to a historical model-based mean ABR of treated bleeds of 18.9 (99% CI: 14.2, 25.2) in patients who received OD therapy
- In children 6 to 11 years old with inhibitors who were previously on OD therapy or without inhibitors who were previously receiving routine prophylaxis, respectively, a model-based mean treated ABR of 1.3 and 1.4 and a median ABR of 1.0 and 1.0 were observed.
The most commonly reported adverse reactions (≥2%) in adult and pediatric patients 6 years of age and older with or without inhibitors were injection site reaction, headache, pyrexia, arthralgia, diarrhea, pruritus, and rash. Thromboembolic events (venous and arterial) in two patients were observed among a total of 259 patients who received HYMPAVZI in the open-label extension study. Thromboembolic events, hypersensitivity, embryofetal toxicity, and increased laboratory values of fibrin D-dimer and prothrombin fragment 1.2 are noted within the Warnings and Precautions section of the U.S. label.
This HYMPAVZI application was reviewed under FDA Priority Review, which is granted to medicines that treat a serious condition and provide a significant improvement in safety or effectiveness over available therapy. The FDA also granted HYMPAVZI Breakthrough Therapy Designation for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in younger pediatric (≥6 to <12 years of age) patients with hemophilia B with and without inhibitors. The FDA's Breakthrough Therapy Designation is intended to expedite the development and review of medicines with the potential to treat a serious or life-threatening disease when preliminary clinical evidence indicates the medicine may demonstrate substantial improvement on a clinically significant endpoint over available therapies.
About HYMPAVZI
Discovered and developed 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 anticoagulants, which acts to inhibit the initiation of blood clotting. By targeting the Kunitz 2 domain of TFPI, HYMPAVZI may help re-establish balance between bleeding and coagulation (or hemostasis) with the goal of offering a combination of bleed protection and straightforward administration.
In 2024, HYMPAVZI became the first anti-TFPI approved in the U.S. and EU for the treatment of hemophilia A or B and it is the first hemophilia medicine approved in the U.S. and EU to be administered via a pre-filled auto-injector pen. HYMPAVZI is a subcutaneous treatment option with a once-weekly dosing schedule and minimal preparation required for each individual administration.
Recently, the European Commission (EC) granted marketing authorization for HYMPAVZI for the routine prophylaxis of bleeding episodes in 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. Pfizer is continuing to pursue expanded regulatory approvals for HYMPAVZI in other countries around the world in this indication. To date, HYMPAVZI 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.
Pfizer Hemophilia Connect offers personalized support for eligible patients in the U.S. prescribed through a Patient Case Manager, patient support resources, benefits verification, and information about the insurance coverage process. Eligible patients prescribed HYMPAVZI can call 1-888-733-2030. Full terms and conditions are available on www.pfizerhemophiliasupport.com/hympavziextlink label.
About the BASIS Clinical Trial
