WHAT COULD THE FUTURE HOLD?
See how researchers aim to tackle unspoken trade-offs and hemostasis In hemophilia A1
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 effective hemostasis.2
FVIII replacement, FVIII mimetics, and gene therapy assist in better clotting.3,4 Natural anticoagulants such as 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.2,3
APC=activated protein C; AT=antithrombin; FVIII=Factor VIII; FX=Factor X; PS=protein S; TFPI=tissue factor pathway inhibitor
David lives with Hemophilia A
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.
Replaces clotting protein that people with hemophilia A are missing with standard half-life or extended half-life products.5
Limitations of FVIII replacement therapy have driven research into alternatives for FVIIIa function.6,7
Rather than replacing FVIII, FVIII mimetics (bispecific antibodies) bridge FIXa and FX in the coagulation cascade to generate thrombin and allows clots to form.3,8
Researchers are working on optimizing mimetics with the intent to influence thrombin generation capabilities.9,10
Research is ongoing to advance the pharmacokinetic properties of bispecific antibodies, including9,10:
- cofactor activity
- binding affinity
- therapeutic half-life
This research aims to reduce administration challenges.
Anticoagulation inhibition is a strategy that aims to inhibit natural anticoagulant proteins to help minimize potential for bleeding.2,3
Gene therapy is a treatment where a new working gene is introduced into a person’s cells.4
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.4
FIX=Factor IX; FIXa= Factor IXa; FVIIIa=Activated Factor VIII
IS NEAR-NORMAL
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.11,12
Reduced thrombin generation,
independent of FVIII activity level, has been associated with a more severe bleeding phenotype.13
Depending on the class of therapy,
thrombin generation may be one way to measure hemostatic success.2,14
What role does thrombin generation play in achieving near-normal hemostasis?
DOSING FREQUENCY IS
IMPORTANT
IN HEMOPHILIA MANAGEMENT, INCLUDING WHEN ADHERING TO A DOSING REGIMEN, ACCORDING TO SOME PATIENTS.15,16
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.9
Bentlee lives with hemophilia A (and mom Teilei)
References
- Data on file. Novo Nordisk Inc; Plainsboro, NJ
- 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.
- Frequently Asked Questions. NBDF. National Bleeding Disorders Foundation. Accessed February 4, 2025. https://www.bleeding.org/bleeding-disorders-a-z/treatment/future-therapies/frequently-asked-questions
- 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.
- Swan D, Mahlangu J, Thachil J. Non-factor therapies for bleeding disorders: a primer for the general haematologist. EJHaem. 2022;3(3):584-595.
- Ozelo MC, Yamaguti-Hayakawa GG. Impact of novel hemophilia therapies around the world. Res Pract Thromb Haemost. 2022;6(3):e12695.
- Current Treatments. NBDF. National Bleeding Disorders Foundation. Accessed September 8, 2024.https://www.bleeding.org/bleeding-disorders-a-z/treatment/current-treatments
- 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.
- ALTUVIIIO® Prescribing Information. Bioverativ Therapeutics Inc. Waltham, MA.
- 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.
- 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.
- Tischer B, Marino R, Napolitano M. Patient preferences in the treatment of hemophilia A: impact of storage conditions on product choice. Patient Prefer Adherence. 2018;12:431-441.
- Thornburg CD, Duncan NA. Treatment adherence in hemophilia. Patient Prefer Adherence. 2017;11:1677-1686.
