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Concizumab & Marstacimab (Alhemo & Hympavzi)

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 16 September 2026Funding No ads, no affiliate links, no vendor payment

Concizumab and marstacimab are two independently developed monoclonal antibodies that treat hemophilia A and B by a genuinely different route than this site's efanesoctocog-alfa-emicizumab page describes — instead of replacing a missing clotting factor or bridging around it, both drugs block tissue factor pathway inhibitor (TFPI), the body's own brake on early clot formation, rebalancing the coagulation cascade rather than patching it. Both reached the US market within three months of each other in late 2024 — concizumab (Novo Nordisk's Alhemo, 20 December 2024) for patients with inhibitors, marstacimab (Pfizer's Hympavzi, 11 October 2024) for patients without them — and both have since expanded to cover the opposite population too. Concizumab's road there was rockier: its Phase 3 program was paused worldwide for a year in 2020 after real thrombotic events in three patients, a genuine safety scare this page covers directly rather than glossing over.

On this page
  1. A third route to fixing hemophilia's clotting cascade
  2. Concizumab: real efficacy, and a real 2020 clinical hold
  3. Marstacimab: a cleaner path in, then a fast label expansion
  4. The same class-wide risk: too much clotting, not too little
  5. Current status

In brief

Should you care? Relevant if you're comparing hemophilia A or B treatment options alongside this site's efanesoctocog alfa & emicizumab page — these are the first two anti-TFPI antibodies approved anywhere, a genuinely new hemophilia drug class rather than a new factor product.

The short version

  • What they are: humanized monoclonal antibodies against tissue factor pathway inhibitor (TFPI), the body's own natural anticoagulant — blocking it shifts coagulation back toward clotting, working in hemophilia A or B, with or without factor-VIII/IX inhibitors, since neither drug depends on factor VIII or IX at all.
  • Evidence: concizumab's Phase 3 explorer7 trial cut the annualized bleeding rate from 11.8 to 1.7 episodes against no prophylaxis (86% reduction, P<0.001) in patients with inhibitors; marstacimab's Phase 3 BASIS trial cut it by 92% against on-demand treatment and 35% against patients' own prior routine prophylaxis in patients without inhibitors.
  • The real story: Novo Nordisk paused concizumab's entire Phase 3 program worldwide in March 2020 after two arterial and three venous thrombotic events in three patients — a real clinical hold, not a rumor — before risk-mitigation measures let trials resume in 2021 and both drugs reached approval.

A third route to fixing hemophilia's clotting cascade

This site's efanesoctocog alfa & emicizumab page covers two ways of treating hemophilia A: supplying more factor VIII directly, or bridging around a missing factor VIII with a bispecific antibody that does its job. Concizumab and marstacimab take a third approach entirely, and one that works for hemophilia B as well as A: both are humanized monoclonal antibodies that bind and block tissue factor pathway inhibitor (TFPI), a protein the body itself produces to restrain the earliest step of clot formation. With TFPI blocked, more tissue factor/factor VIIa complex stays active, driving more factor Xa production and shifting the coagulation balance back toward clotting — a mechanism that works regardless of whether the patient is missing factor VIII (hemophilia A) or factor IX (hemophilia B), and regardless of whether they've developed inhibitor antibodies against replacement factor, since neither drug is a clotting factor for the immune system to neutralize. Novo Nordisk's concizumab (Alhemo) and Pfizer's marstacimab (Hympavzi) are unrelated antibodies from separate development programs that arrived at the same TFPI-blocking strategy independently, making this a genuinely new hemophilia drug class with two competing entrants rather than one company's invention and a follow-on copy.

Concizumab: real efficacy, and a real 2020 clinical hold

Concizumab's pivotal evidence came from the Phase 3 explorer7 trial in patients with hemophilia A or B and factor inhibitors: 133 patients were assigned to no prophylaxis, concizumab prophylaxis, or (for those already on concizumab in an earlier trial) continued concizumab. The estimated mean annualized bleeding rate was 11.8 episodes on no prophylaxis versus 1.7 on concizumab prophylaxis — a rate ratio of 0.14, an 86% reduction (95% CI 0.07-0.29, P<0.001) — with a median annualized bleeding rate of 0 across the pooled concizumab-treated groups (Matsushita T, Shapiro A, Abraham A, et al., "Phase 3 Trial of Concizumab in Hemophilia with Inhibitors," N Engl J Med 2023;389(9):783-794, PMID 37646676, DOI: 10.1056/NEJMoa2216455).1 That trial result came after a genuine interruption: in March 2020, Novo Nordisk paused explorer7, explorer8 and a Phase 2 study worldwide after two arterial and three venous thrombotic serious adverse events occurred in three patients, all of whom had pre-existing thrombotic risk factors and had used concomitant hemostatic medication around the time of the event; the FDA followed with its own clinical hold. Novo Nordisk and independent investigators spent roughly a year investigating the events, implementing risk-mitigation measures and updating trial protocols — including a revised dosing regimen and tighter guidance for managing breakthrough bleeds — before the clinical hold was lifted and treatment resumed in 2021. The FDA approved concizumab as Alhemo on 20 December 2024 (BLA 761315) for hemophilia A or B with inhibitors in patients 12 and older; the European Commission had approved it for the same population on 13 December 2024. On 31 July 2025, the FDA expanded the US label to cover hemophilia A or B without inhibitors as well (still ages 12 and older), based on the companion Phase 3 explorer8 trial, which found reductions of 86% and 79% in annualized bleeding rate for hemophilia A and B respectively without inhibitors, against no prophylaxis.

Marstacimab: a cleaner path in, then a fast label expansion

Marstacimab's development had no comparable safety pause. Its pivotal evidence came from the Phase 3 BASIS trial, an open-label study in patients 12 to 74 years old with severe hemophilia A or moderately severe to severe hemophilia B without inhibitors: patients previously on on-demand treatment saw their annualized bleeding rate fall from 39.9 to 3.2 after switching to once-weekly marstacimab (a 92% reduction), and patients previously on routine factor prophylaxis saw theirs fall from 7.9 to 5.1 (a 35% reduction, meeting both non-inferiority and superiority thresholds against their own prior prophylaxis) (Matino D, Palladino A, Taylor CT, et al., "Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial," Blood 2025;146(14):1654-1663, PMID 40608864, DOI: 10.1182/blood.2024027468).2 The FDA approved marstacimab as Hympavzi on 11 October 2024 (BLA 761369) for hemophilia A or B without inhibitors in patients 12 and older — Pfizer's own materials call it the first and only anti-TFPI antibody approved in the US, and the first hemophilia medicine delivered via a prefilled auto-injector pen. A parallel BASIS cohort in patients with inhibitors, run alongside the main trial, found a 93% reduction in annualized bleeding rate against on-demand bypassing-agent treatment (Blood 2026;147(9):920-931, DOI: 10.1182/blood.2025031065)3 — and on 8 June 2026, the FDA approved marstacimab for hemophilia A or B with inhibitors too, alongside a second expansion down to patients as young as 6 (with or without inhibitors), based on that with-inhibitors cohort and the separate Phase 3 BASIS KIDS pediatric trial (NCT05611801).

The same class-wide risk: too much clotting, not too little

Blocking an anticoagulant carries a mechanism-specific risk

Because both drugs work by removing one of the body's own brakes on clotting, the predictable flip side of their efficacy is a real risk of too much clotting rather than too little. Neither drug's US label carries a boxed warning, but both carry a specific warnings-and-precautions section for venous and arterial thromboembolism. Across concizumab's clinical trial program, venous and arterial thromboembolic events were reported in about 1.9% of patients (6 of 320), each with other identifiable risk factors present. Marstacimab's pivotal BASIS trials recorded no thromboembolic events at all; one non-life-threatening deep-vein thrombosis was later reported in its long-term open-label extension, in a patient with multiple pre-existing prothrombotic risk factors after roughly three years of treatment — a real event, but a markedly smaller signal so far than concizumab's. Concizumab's label goes further, requiring a plasma-concentration check by an FDA-authorized ELISA test four weeks after starting treatment and cautioning that routine coagulation biomarkers may not reliably signal an evolving clot the way they would on a factor-replacement therapy — a genuine monitoring wrinkle specific to this mechanism. Both labels advise pausing treatment and using the minimum effective dose of any factor product or bypassing agent given alongside it, and both recommend stopping treatment roughly a week before major surgery. This is a real, drug-class-specific safety consideration for a treating hematologist to manage, not a reason on its own to avoid either drug — the same 2020 clinical-hold investigation that paused concizumab is also the reason its current dosing and monitoring protocol exists in the form it does today.

Current status

Both Alhemo and Hympavzi remain FDA-approved and are actively marketed — Alhemo by Novo Nordisk, Hympavzi by Pfizer — each now covering hemophilia A and B, with and without inhibitors, following concizumab's July 2025 and marstacimab's June 2026 label expansions. Hympavzi additionally reaches down to age 6, while Alhemo remains approved from age 12 up as of this review. The two compete directly with each other on dosing frequency (concizumab daily, marstacimab weekly) and with the older efanesoctocog alfa/emicizumab options this site covers separately, giving hemophilia patients and their hematologists a genuinely wider set of non-factor-replacement choices than existed before 2024.

References

  1. Matsushita T, Shapiro A, Abraham A, Angchaisuksiri P, Castaman G, Cepo K, Dhalluin C, Escobar M, Hermans C, Jiménez-Yuste V, Klamroth R, Kruse-Jarres R, Mancuso ME, Miesbach W, Oldenburg J, Wheeler A, Skov M, Chowdary P, "Phase 3 Trial of Concizumab in Hemophilia with Inhibitors," N Engl J Med 2023;389(9):783-794, PMID 37646676, DOI: 10.1056/NEJMoa2216455 — explorer7 trial; annualized bleeding rate 11.8 (no prophylaxis) vs. 1.7 (concizumab), rate ratio 0.14, P<0.001.
  2. Matino D, Palladino A, Taylor CT, et al., "Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial," Blood 2025;146(14):1654-1663, PMID 40608864, DOI: 10.1182/blood.2024027468 — annualized bleeding rate reduced 92% vs. on-demand treatment, 35% vs. prior routine prophylaxis.
  3. "Efficacy and safety of marstacimab prophylaxis in hemophilia A/B with inhibitors: results from the phase 3 BASIS trial," Blood 2026;147(9):920-931, PMID 41351884, DOI: 10.1182/blood.2025031065 — 93% annualized-bleeding-rate reduction vs. on-demand bypassing-agent treatment in the with-inhibitors cohort, no thromboembolic events.
  4. FDA approval of Alhemo (concizumab-mtci, BLA 761315, Novo Nordisk), 20 December 2024, for hemophilia A/B with inhibitors ages 12+; European Commission approval, 13 December 2024 (EU number EMEA/H/C/005938); Novo Nordisk announcement of the worldwide pause of explorer5/7/8 trials, 16 March 2020, following two arterial and three venous thrombotic serious adverse events in three patients — cross-checked against ASH Clinical News and Hemophilia News Today contemporaneous coverage; FDA label expansion of concizumab to hemophilia A/B without inhibitors ages 12+, 31 July 2025, based on the Phase 3 explorer8 trial (86% ABR reduction in hemophilia A, 79% in hemophilia B, both without inhibitors, versus no prophylaxis).
  5. FDA approval of Hympavzi (marstacimab-hncq, BLA 761369, Pfizer), 11 October 2024, for hemophilia A/B without inhibitors ages 12+; FDA approval of the expanded Hympavzi indication covering hemophilia A/B with inhibitors and ages 6+, 8 June 2026, based on the BASIS with-inhibitors cohort and the Phase 3 BASIS KIDS pediatric trial (NCT05611801) — cross-checked against Pfizer's own press releases and contemporaneous trade coverage (Hematology Advisor, AJMC, Contemporary Pediatrics). National Bleeding Disorders Foundation MASAC document on anti-TFPI agents in hemophilia (adopted March 2025, last reviewed September 2025), reporting venous/arterial thromboembolic events in 1.9% (6/320) of concizumab clinical-trial patients versus no thromboembolic events in marstacimab's pivotal BASIS trials and one deep-vein thrombosis in a risk-factor-positive patient in marstacimab's long-term open-label extension — cross-checked against current FDA-approved prescribing information for both Alhemo and Hympavzi, current as of this review.