FDA expands marstacimab (HYMPAVZI) approval to children ages 6–11 and hemophilia patients with inhibitors

Children as young as 6 years old and patients whose hemophilia is complicated by inhibitors now have access to a once-weekly subcutaneous non-factor prophylactic option following an expanded FDA approval of marstacimab-hncq (Hympavzi; Pfizer). The agency approved the supplemental biologics license application under Priority Review, broadening the drug's U.S. indication to cover adults and pediatric patients 6 years and older with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency) with or without inhibitors.¹

"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, MD, director of the 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."

Disease burden and unmet need in hemophilia A and B with inhibitors

Hemophilia affects more than 800,000 people worldwide and is typically diagnosed in early childhood.¹ The disorder's hallmark—impaired clot formation—places patients at risk for painful spontaneous and traumatic bleeds, particularly hemarthroses that can permanently damage growing cartilage and bone in pediatric joints.¹ Factor replacement therapy has historically been the standard of care, but it requires frequent intravenous infusions, a significant barrier to adherence for some patients.²

A particularly difficult-to-treat subset develops neutralizing antibodies—inhibitors — to exogenous factor concentrates. Inhibitors arise in approximately 20% of patients with hemophilia A and 3% of those with hemophilia B.¹ For these patients, factor replacement loses efficacy, leaving bypassing agents as the primary rescue option. Many patients refractory to immune tolerance induction lack reliable prophylactic coverage.¹ The expanded approval is especially notable for children ages 6 to 11 with hemophilia B: marstacimab is now the first subcutaneous non-factor therapy available to this age group.¹

BASIS and BASIS KIDS trial design and efficacy data

The adult and adolescent inhibitor data came from the open-label Phase 3 BASIS trial (NCT03938792), which enrolled patients ages 12 to younger than 75 years with severe hemophilia A (FVIII <1%) or moderately severe to severe hemophilia B (FIX ≤2%) and inhibitors.¹ The inhibitor cohort included 48 participants who received prophylaxis, a 300 mg subcutaneous loading dose followed by 150 mg once weekly, during a 12-month active treatment period, compared with a 6-month observational period on on-demand intravenous bypassing agents.¹
Marstacimab demonstrated superiority on the primary endpoint: mean treated annualized bleeding rate (ABR) was reduced by 93% compared with on-demand bypass therapy (ABR 1.4 [95% CI, 0.9–2.3] vs 19.8 [95% CI, 16.1–24.3]; P <.0001).^1,3

The pediatric expansion was supported by interim data from BASIS KIDS (NCT05611801), a global open-label Phase 3 study enrolling children ages 1 to 17 years with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors.¹ Among 57 patients ages 6 to 17 who received marstacimab — including 34 children ages 6 to 11 — those in the younger cohort received a 150 mg loading dose followed by 75 mg subcutaneously once weekly.¹

Marstacimab was associated with low annualized bleeding rates across pediatric patient groups. Children without inhibitors had a mean treated ABR of 1.8, compared with a historical estimate of 3.6 for routine prophylaxis. Among children with inhibitors, the mean treated ABR was 1.4 vs a historical estimate of 18.9 for on-demand treatment. In children aged 6 to 11 years previously treated with either on-demand therapy or routine prophylaxis, model-based mean treated ABRs ranged from 1.3 to 1.4, with median ABRs of 1.0 in both cohorts.

Marstacimab mechanism of action and prior regulatory history

Marstacimab targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulant that suppresses the extrinsic coagulation pathway.¹ By blocking TFPI, marstacimab works independently of factors VIII and IX, which makes the mechanism applicable across hemophilia A, hemophilia B, and inhibitor-complicated disease alike. This differentiates it from factor replacement therapies and from emicizumab, which acts as a factor VIII mimetic and is not active in hemophilia B.

Marstacimab was first approved in the United States and European Union in 2024 for adults and adolescents 12 years and older without inhibitors, making it the first anti-TFPI agent and the first hemophilia therapy delivered via a prefilled auto-injector pen approved in either jurisdiction.^1,2 The current expansion extends that approval to patients with inhibitors and to younger children, with Pfizer noting it has received approvals in more than 40 countries for the inhibitor-free population.¹

Limitations, safety considerations, and next steps

The BASIS KIDS data supporting the pediatric expansion are interim and descriptive, without formal hypothesis testing in the youngest age cohort. The open-label designs of both BASIS and BASIS KIDS, and the use of historical comparators rather than concurrent randomized controls, limit causal inference and introduce potential for bias.⁴ Generalizability to patients with moderate hemophilia or those with milder inhibitor titers warrants further study.

Safety data pooled from 259 patients across open-label extension studies identified thromboembolic events — venous and arterial — in 2 patients.¹ Prescribers should note warnings for thromboembolic events, hypersensitivity, embryofetal toxicity, and elevated fibrin D-dimer and prothrombin fragment 1.2 values.¹ The most common adverse reactions (≥2%) were injection site reaction, headache, pyrexia, arthralgia, diarrhea, pruritus, and rash.¹ Pfizer continues to pursue regulatory approvals for the inhibitor and pediatric indications in additional countries.

References

1. Pfizer Inc. U.S. FDA Approves Pfizer’s HYMPAVZI for the Treatment of Two Additional Hemophilia A or B Patient Populations with Significant Medical Need. Press release. June 8, 2026. Accessed June 8, 2026. https://www.businesswire.com/news/home/20260608815972/en/U.S.-FDA-Approves-Pfizers-HYMPAVZI-for-the-Treatment-of-Two-Additional-Hemophilia-A-or-B-Patient-Populations-with-Significant-Medical-Need

2. Shapiro AD, Angchaisuksiri P, Astermark J, et al. Subcutaneous marstacimab prophylaxis in hemophilia A and B without inhibitors: the Phase 3 BASIS study. Blood. 2023. doi:10.1182/blood.2023023010

3. Young G, Mahlangu J, Kenet G, et al. Marstacimab in hemophilia with inhibitors: Phase 3 BASIS trial results. N Engl J Med. Presented at ASH Annual Meeting, 2024.

4. ClinicalTrials.gov. BASIS KIDS: A clinical trial of marstacimab in pediatric patients with hemophilia A or B. NCT05611801. Accessed June 5, 2026. https://clinicaltrials.gov/study/NCT05611801