The US Food and Drug Administration approved an expanded indication for marstacimab-hncq (HYMPAVZI) for routine prophylaxis in patients aged 12 years and older with hemophilia A or B with inhibitors and pediatric patients aged 6 to 11 years with or without inhibitors, according to a press release from Pfizer.
HYMPAVZI is now indicated for adults and pediatric patients aged 6 years and older with hemophilia A (congenital factor VIII deficiency) or hemophilia B (congenital factor IX deficiency), with or without inhibitors. The treatment is administered once weekly by subcutaneous injection and does not require routine treatment-related laboratory monitoring. This approval makes HYMPAVZI the first subcutaneous non-factor therapy available for pediatric patients with hemophilia B aged 6 to 11 years.
According to Pfizer, the expanded approval was based on data from the phase 3 BASIS and BASIS KIDS trials.
In the inhibitor cohort of the phase 3 BASIS trial, which included adolescents and adults aged 12 years and older with hemophilia A or B, marstacimab reduced the mean treated annualized bleeding rate (ABR) by 93% compared with on-demand intravenous treatment with bypassing agents (products such as activated prothrombin complex concentrates or recombinant factor VIIa). The mean treated ABR was 1.4 (95% CI: 0.9-2.3) among patients who received marstacimab compared with 19.8 (95% CI: 16.1-24.3) among those who received on-demand treatment (p<0.0001), meeting the trial's formal superiority endpoint.
Interim results from the phase 3 BASIS KIDS trial included patients aged 6 to 17 years with hemophilia A or B with or without inhibitors. These results reflect descriptive analyses — not inferential comparisons — and the reference rates are historical model-based estimates rather than concurrent control arms. Among patients without inhibitors, the mean treated ABR was 1.8 (99% CI: 1.1-2.6) among patients who received marstacimab compared with a historical model-based rate of 3.6 (99% CI: 1.3-5.8) among patients receiving routine prophylaxis. Among patients with inhibitors, the mean treated ABR was 1.4 (99% CI: 0.5-4.5) compared with a historical model-based rate of 18.9 (99% CI: 14.2-25.2) among patients receiving on-demand therapy.
Dosing in BASIS KIDS differed by age group. Patients aged 6 to 11 years received a 150 mg subcutaneous loading dose followed by 75 mg once weekly, while patients aged 12 to 17 years received a 300 mg loading dose followed by 150 mg once weekly.
Marstacimab works through a mechanism distinct from factor replacement therapies. Rather than replacing deficient clotting factors, it targets the Kunitz 2 domain of tissue factor pathway inhibitor (TFPI), a natural anticoagulant that regulates the initiation of coagulation. By inhibiting TFPI at this domain, marstacimab aims to restore balance between bleeding and coagulation, according to Pfizer.
The most commonly reported adverse reactions (2% or greater) were injection-site reactions, headache, pyrexia, arthralgia, diarrhea, pruritus, and rash. The prescribing information includes warnings regarding thromboembolic events — which occurred in 2 of 259 patients in the open-label extension study — hypersensitivity reactions, embryofetal toxicity, and increased laboratory values of fibrin D-dimer and prothrombin fragment 1.2.
The application was reviewed under FDA Priority Review. HYMPAVZI also previously received Breakthrough Therapy Designation for younger pediatric patients aged 6 to under 12 years with hemophilia B with or without inhibitors.
Source: Pfizer