Pfizer announced that the US 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 aged 12 years and older with inhibitors and pediatric patients (aged 6 to 11 years) with or without inhibitors.

HYMPAVZI is now indicated in the US 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.

Guy Young, MD, Director, Hemostasis and Thrombosis Center, Children's Hospital, Los Angeles, said, “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. 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. 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. Children’s joints have growing cartilage and bone, which makes them particularly susceptible to damage caused by repeated bleeding episodes.

Inhibitors to factor replacement therapy limit treatment options for people living with hemophilia and are associated with an increased risk of uncontrolled bleeding. These inhibitory antibodies develop in approximately 20 percent of those with hemophilia A and 3 percent of those with hemophilia B. 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.

Aamir Malik, Chief US Commercial Officer and Executive Vice President (EVP), Pfizer, said, “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 aged 6 years and older. Particularly for children aged 6 to 11 with hemophilia B who will now, for the first time, have a subcutaneous non-factor treatment available. 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 (NCT03938792) 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 Annualised Bleeding Rate (ABR) by 93 percent compared to On-Demand (OD) intravenous treatment with bypassing agents (1.4 [95 percent CI: 0.9-2.3] vs.19.8 [95 percent CI: 16.1-24.3]; p<0.0001).

Interim results from the phase 3 BASIS KIDS trial (NCT05611801) supported the approval of HYMPAVZI in children aged 6 to 17 years with hemophilia A or B with or without inhibitors. Descriptive analyses, which summarise trends in the data, in patients who received HYMPAVZI demonstrated that in children aged 6 to 17 years old without inhibitors, a mean treated ABR of 1.8 (99 percent 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 percent CI: 1.3-5.8) in patients who received routine prophylaxis; in children aged 6 to 17 years old with inhibitors, a mean treated ABR of 1.4 (99 percent 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 percent CI: 14.2, 25.2) in patients who received OD therapy; and in children aged 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 (ARs) (≥2 percent) 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 US label.

This HYMPAVZI application was reviewed under FDA Priority Review (PR), 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.