WHAT COULD THE FUTURE HOLD?

See how researchers aim to tackle unspoken trade-offs and hemostasis In hemophilia A^1,2

Nikola lives with hemophilia A.

TREATING HEMOPHILIA A

The goal of all current and investigational hemophilia therapies, from FVIII replacement to nonfactor therapies, is to restore thrombin generation to achieve hemostasis.³

FVIII replacement, FVIII mimetics, and gene therapy assist in better clotting.^4,5 Natural anticoagulants such as or including TFPI, APC, PS, and AT play a role in inhibiting thrombin generation or function at various points in the coagulation cascade. Targeting these anticoagulant proteins with hemophilia therapies aims to promote hemostasis.^3,4

APC=activated protein C; AT=antithrombin; FVIII=Factor VIII; PS=protein S; TFPI=tissue factor pathway inhibitor.

David lives with hemophilia A.

IN ADDITION TO CLINICAL TRIAL RESULTS, CONSIDER THE FOLLOWING COAGULATION MARKERS WHEN ASSESSING NONFACTOR THERAPIES FOR HEMOPHILIA A

Thrombin generation

Hemostasis depends on thrombin generation³

Restoring sufficient thrombin generation to form stable blood clots should be a goal of all hemophilia therapies³

Clot formation

Higher thrombin activity was associated with a strong fibrin structure, while lower thrombin activity was associated with a weak fibrin structure⁶

FVIII equivalence

FVIII-equivalent activity is an estimated comparison to FVIII activity levels that may help contextualize hemostatic protection, but it does not establish pharmacokinetic, pharmacodynamic, or clinical equivalence to FVIII replacement therapy^7,8

Thrombin generation assays are often used in nonfactor clinical trials to assess FVIII equivalence⁹

Hemophilia Treatment Strategies of Today

—and ONGOING RESEARCH FOR Tomorrow

Click the expanders below to learn more about current and investigational hemophilia treatment approaches and what they could mean for your patients.

FVIII MIMETICS

Rather than replacing FVIII, FVIII mimetics (bispecific antibodies) bridge FIXa and FX in the coagulation cascade to generate thrombin and allows clots to form.^10,11

Researchers are working on optimizing mimetics with the intent to influence thrombin generation capabilities.^12,13

Research is ongoing to advance the pharmacokinetic properties of bispecific antibodies, including^12,13:

cofactor activity
binding affinity
therapeutic half-life

This research aims to reduce administration challenges.

FVIII REPLACEMENT

Replaces clotting protein that people with hemophilia A are missing with standard half-life or extended half-life products.¹⁰

Limitations of FVIII replacement therapy have driven research into alternatives for FVIIIa function.^10,11

ANTICOAGULANT PATHWAY INHIBITION

Anticoagulant pathway inhibition is a strategy that aims to inhibit natural anticoagulant proteins to help minimize potential for bleeding¹⁴

Examples of anticoagulant proteins include tissue factor pathway inhibitor, antithrombin, and the protein C/S pathway.¹⁴

GENE THERAPY

Gene therapy is a treatment where a new working gene is introduced into a person’s cells.¹⁵

In patients with hemophilia A, gene therapy provides a new copy of the FVIII gene to give the body instructions on how to make the missing factor.¹⁵

FIXa=activated Factor IX; FVIIIa=activated Factor VIII; FX=Factor X.

IS ACHIEVING
HEMOSTASIS POSSIBLE?

CERTAIN FVIII REPLACEMENT CAN MAINTAIN

FVIII LEVELS >40% for most of the week, which is in the near-normal range while current FVIII mimetics provide an estimated FVIII level equivalence of approximately 10% to 20%, based on modeling and indirect assays.^11,16

Reduced thrombin generation,

independent of FVIII activity level, has been associated with a more severe bleeding phenotype.¹⁷

Depending on the class of therapy,

thrombin generation may be one way to measure hemostatic success.^3,18

What role does thrombin generation play in achieving hemostasis?

DOSING FREQUENCY IS IMPORTANT

IN HEMOPHILIA MANAGEMENT, INCLUDING WHEN ADHERING TO A DOSING REGIMEN, ACCORDING TO SOME PATIENTS.¹⁹

could fewer infusions or injections help reduce their management challenges?

Researchers are exploring how to design molecules to evolve pharmacokinetics, such as half-life and clearance rates, which may impact dosing regimens.¹²

Bentlee lives with hemophilia A (with mom Teilei).

STAY UP TO DATE
WITH THE LATEST INFORMATION

Get updates and communications on hemophilia A from Novo Nordisk as they become available.

References:

Brod M, Bushnell DM, Neergaard JS, et al. Understanding treatment burden in hemophilia: development and validation of the Hemophilia Treatment Experience Measure (Hemo-TEM). J Patient Rep Outcomes. 2023;7(1):17.
Wheeler AP, Cibelli E, Hanson Get al. Treatment and disease burden in a cohort of people with haemophilia without inhibitors in the United States. Haemophilia. 2025;31(5):912-921.
Sidonio RF Jr, Hoffman M, Kenet G, Dargaud Y. Thrombin generation and implications for hemophilia therapies: a narrative review. Res Pract Thromb Haemost. 2022;7(1):100018.
Ellsworth P, Ma A. Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021;2021(1):219-225.
National Bleeding Disorders Foundation. Frequently Asked Questions. NBDF. Accessed September 16, 2025. https://www.bleeding.org/bleeding-disorders-a-z/treatment/future-therapies/frequently-asked-questions
Mihalko E, Brown AC. Clot structure and implications for bleeding and thrombosis. Semin Thromb Hemost. 2020;46(1):96-104.
Leksa NC, Aleman MM, Goodman AG, Rabinovich D, Peters R, Salas J. Intrinsic differences between FVIIIa mimetic bispecific antibodies and FVIII prevent assignment of FVIII-equivalence. J Thromb Haemost. 2019;17:1044-1052.
Lenting PJ. Laboratory monitoring of hemophilia A treatments: new challenges. Blood Adv. 2020;4:2111-2118.
Manco-Johnson MJ, Warren BB, Buckner TW, Funk SM, Wang M. Outcome measures in haemophilia: beyond ABR (annualized bleeding rate). Haemophilia. 2021;27(suppl 3):87-95.
Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition [published correction appears in Haemophilia. 2021;27(4):699]. Haemophilia. 2020;26(suppl 6):1-158.
Mancuso ME, Croteau SE, Klamroth R. Benefits and risks of non-factor therapies: redefining haemophilia treatment goals in the era of new technologies. Haemophilia. 2024;30(Suppl 3):39-44.
Teranishi-Ikawa Y, Soeda T, Koga H, et al. A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a nonhemophilic state. J Thromb Haemost. 2024;22(2):430-440.
Lillicrap D, Lenting P. Hemophilia A treatment innovation: factor VIII mimetic bispecific antibodies-generational enhancement. J Thromb Haemost. 2024;22(2):352-355.
Callaghan MU, Sidonio R, Pipe SW. Novel therapeutics for hemophilia and other bleeding disorders. Blood. 2018;132(1):23-30.
Butterfield JSS, Hege KM, Herzog RW, Kaczmarek R. A molecular revolution in the treatment of hemophilia. Mol Ther. 2020;28(4):997-1015.
ALTUVIIIO^® Prescribing Information. Bioverativ Therapeutics Inc.; Waltham, MA.
Verhagen MJA, van Balen EC, Blijlevens NMA, et al. Patients with moderate hemophilia A and B with a severe bleeding phenotype have an increased burden of disease. J Thromb Haemost. 2024;22(1):152-162.
Bernardo Á, Caro A, Martínez-Carballeira D, et al. Applicability of the thrombin generation test to evaluate the hemostatic status of hemophilia A patients in daily clinical practice. J Clin Med. 2022;11(12):3345.
Lu H, Gould T, Colavecchia C, et al. Patient and caregiver preferences for long‐term prophylactic treatment of bleeds in haemophilia: a discrete‐choice experiment. Haemophilia. 2026;32(1):116-130.
Thornburg CD, Duncan NA. Treatment adherence in hemophilia. Patient Prefer Adherence. 2017;11:1677-1686.

WHAT COULD THE FUTURE HOLD?

See how researchers aim to tackle unspoken trade-offs and hemostasis In hemophilia A1,2