Pfizer reported new Phase 3 data showing that Hympavzi (marstacimab) reduced treated annualized bleeding rate (ABR) by 93% compared with on-demand bypassing therapy in adults and adolescents with hemophilia A or B with inhibitors. The results, from the BASIS trial (NCT03938792) were presented at this week’s American Society of Hematology (ASH) annual meeting.
The open-label, multicenter trial enrolled 48 participants aged 12–75 who continued to experience bleeds on on-demand therapy. Over a 12-month treatment period, using a 300 mg subcutaneous loading dose followed by 150 mg once weekly, ABR declined from 19.78 to 1.39 bleeds per year. Improvements were consistent across spontaneous bleeds, joint bleeds, target-joint bleeds and total bleeds.
Median ABR fell to zero with Hympavzi prophylaxis, compared with 16.42 under prior on-demand treatment (95% CI: 0.00–14.91 vs. 0.00–69.10). By six months, patients also reported better physical health, reduced pain and improved mobility.
Safety was generally favorable. No deaths or thromboembolic events occurred, and most adverse events were mild or moderate. One treatment-related serious adverse event (skin rash) led to discontinuation and subsequently resolved.
Hympavzi’s positioning in hemophilia therapy
Hympavzi is a Pfizer-discovered antibody targeting tissue factor pathway inhibitor (TFPI), administered once weekly by subcutaneous injection. TFPI regulates the extrinsic coagulation pathway by inhibiting the tissue factor–factor VIIa complex and factor Xa. Blocking TFPI “rebalances” the pathway and enhances thrombin generation even in the absence of FVIII or FIX, offering an alternative to factor-replacement therapy.
The US FDA first approved Hympavzi in October 2024 for routine prophylaxis in hemophilia A or B without inhibitors. It is delivered once weekly via a pre-filled pen, without lab monitoring requirements.
Novo Nordisk’s Alhemo (concizumab), another TFPI-targeting antibody, was first approved in Canada in 2023 and requires daily subcutaneous dosing. The two drugs act on different domains of TFPI: Alhemo binds the Kunitz-2 domain to block inhibition of factor Xa, while Hympavzi targets the Kunitz-1 domain, preventing inhibition of the tissue factor–factor VIIa complex.
Pfizer said it will now seek US FDA and EMA approval for Hympavzi in inhibitor-positive hemophilia A or B, positioning the therapy as a potentially transformative prophylactic option for this high-need population.