FDA approves Hympavzi for the Treatment of Two Additional Hemophilia A or B Patient Populations with Significant Medical Need – Pfizer

Pfizer Inc. announced that the 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. 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% of those with hemophilia A and 3% 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.

“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 (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 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 (NCT05611801) 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:

• i) 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
• ii) 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
• iii) 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 the BASIS Clinical Trial 
The pivotal BASIS study is a global, Phase 3, open-label, multicenter study to evaluate the efficacy data and safety profile of Hympavzi in adolescent and adult participants ages 12 to <75 years with severe hemophilia A (defined as FVIII <1%) or moderately severe to severe hemophilia B (defined as FIX activity ≤2%) with or without inhibitors. The inhibitor cohort included 48 people living with hemophilia with inhibitors who were treated with Hympavzi during a 12-month active treatment period (ATP) versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in a six-month observational period. During the ATP, participants received prophylaxis (a 300 mg subcutaneous loading dose of Hympavzi, followed by 150 mg subcutaneously once weekly) An additional three patients in the inhibitor cohort were on routine prophylactic treatment prior to the study and not included in the primary efficacy analysis. The primary endpoint measures the treated ABR (annualized bleeding rate) during the 12-month ATP with Hympavzi compared to treated ABR on prior on-demand bypass therapy.

About the BASIS KIDS Clinical Trial 
The BASIS KIDS study is a global, Phase 3, open-label study investigating the safety and efficacy of Hympavzi in children 1 to 17 years of age with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors. In the analysis, 57 patients ages 6 to 17 years old – including 34 patients between ages 6 to 11 – received Hympavzi during a 12-month ATP versus routine prophylaxis with factor replacement therapy (without inhibitor), or routine prophylaxis or on-demand treatment with bypassing agents (with inhibitor), administered as part of usual care in a 12-month period prior to enrollment. During the ATP participants in the 6 to 11 age group, received prophylaxis (a 150 mg subcutaneous loading dose of Hympavzi, followed by 75 mg subcutaneous once weekly) while participants in the 12 to 17 age group received prophylaxis (a 300mg subcutaneous loading dose of Hympavzi followed by 150 mg subcutaneously once weekly). The primary endpoint measures treated ABR during the 12-month ATP with Hympavzi compared to ABR on prior routine prophylaxis with factor replacement therapy, or routine prophylaxis or on-demand treatment with bypassing agents.