Intended for US Healthcare Professionals Only

Around one in three previously untreated hemophilia A patients develops neutralizing antibodies (inhibitors) against factor VIII (FVIII), rendering therapy ineffective.1-3 This is the most serious and challenging complication of FVIII therapy in hemophilia A.2 The resulting resistance to therapeutic FVIII may have major adverse consequences for disease management and outcomes.4

1 in 3 previously untreated hemophilia A patients develop inhibitors

Immune Tolerance Induction: A Proven Tool for Inhibitor Management

Immune tolerance induction (ITI) is the only proven approach for eradicating inhibitors and increasing patient tolerance to FVIII. The treatment involves prolonged, daily exposure to high-dose FVIII.5 ITI has been shown to eradicate inhibitors in 60%-90% of patients with hemophilia A.5

ITI Effectiveness%

ITI has been shown to eradicate inhibitors in 60%-90% of patients with hemophilia A

The success rate of ITI may vary depending on patient variables and factors relating to the pattern of treatment for the induction of immune tolerance.6

Both plasma-derived (pd) or recombinant (r) FVIII ITI are recommended as the primary treatment option to eradicate inhibitors in both European and US guidelines.4,5

However, some recent studies on both children and adults suggest that using pdFVIII with a high presence of von Willebrand factor (VWF) may exert an immunoprotective effect on the FVIII, which may consequently have a positive impact on the success of the ITI.6,7,8

Favorable Risk Factors for ITI Success5

Consistently recognized predictors of ITI success

Peak historical inhibitor titer ≤200 BU/mL

Inhibitor titer <10 BU/mL before ITI initiation

Peak inhibitor titer during ITI ≤200 BU/mL

Other predictors of better ITI outcomes

Age <8 years at start of ITI

ITI initiated <5 years after inhibitor diagnosis

Interruptions in ITI <2 weeks in duration

Typical ITI Dosing5

For young patients (age <8 years) with adequate venous access and favorable risk factors

Lower-dose regimen favored by many US HTCs

  • Lower-dose regimens are supported by cohort and registry data; no randomized clinical trials. HTCs may use internal protocols and guidelines for higher-dose regimens
  • MASAC (Medical and Scientific Advisory Council) recommendations on concomitant use of Hemlibra® (emicizumab) during ITI suggest no more than 50 IU/kg per dose be administered unless observation occurs within a clinical trial9

Using wilate for ITI Therapy

wilate® is a high-purity human pdFVIII/VWF concentrate containing the native FVIII/VWF complex
in a physiological 1:1 ratio.10 A recent study reports favorable results using wilate® for ITI in children
with severe hemophilia A with inhibitors.4

Study design4

Conducted in 11 severe hemophilia A patients with inhibitors

  • 2 patients were treated with wilate® for rescue ITI (previous ITI treatment was unsuccessful)
  • All but 1 patient had at least one poor prognosis factor for ITI outcome

All but 3 patients were less than 6 years of age at onset of ITI with wilate®

Titers were measured prior to and during ITI (Nijmegen-Bethesda)

Patients were treated with wilate ITI doses of 50-60 IU/kg, 3x/week, and up to 200 IU/kg/day

Outcomes

  • Complete or partial success in 9 of 11 (82%) patients — including two patients who received rescue ITI4
Patient ITI Dose Undetectable Inhibitor ITI Outcome
1 200 IU/kg/day Yes Partial response
2 100 IU/kg/day Yes Complete success
3 100 IU/kg/day No Failure
4 100 IU/kg/day, 70 IU/kg/dayᵃ Yes Complete success
5 50-60 IU/kg 3x/wk Yes Complete success
6 50-60 IU/kg 3x/wk Yes Complete success
7* 100 IU/kg/day Yes Complete success
8 100 IU/kg/day No Failure
9* 100 IU/kg/day Yes Partial success
10 94 IU/kg/day Yes Partial success
11 90 IU/kg/day Yes Complete success

Complete ITI success: <0.6 BU/mL; FVIII recovery ≥66% of predicted; FVIII half-life ≥6 hrs

Partial ITI success: Achievement of two of the three above criteria

Partial ITI response: Achievement of one of the three above criteria

Failure of ITI: No achievement of any of the above criteria within 33 months of starting ITI

*Rescue ITI (previous ITI had been unsuccessful in these patients).
aDose tapering once tolerance was successful.

  • Low bleeding rates while on wilate® ITI4
  • Median ABR (annual bleed rate) decreased by 35% during ITI with wilate compared with the time with inhibitors before ITI.
  • 1

    Vézina, C., Carcao, M., Infante‐Rivard, C., Lillicrap, D., Stain, A.M., Paradis, E., Teitel, J., Rivard, G.E. and (2014), Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010. Haemophilia, 20: 771-776. doi:10.1111/hae.12479

  • 2

    Xi, M, Makris, M, Marcucci, M, Santagostino, E, Mannucci, PM, Iorio, A. Inhibitor development in previously treated hemophilia A patients: a systematic review, meta‐analysis and meta‐regression. J Thromb Haemost 2013; 11: 1655– 62. DOI:10.1111/jth.12335.

  • 3

    Blanchette, VS, Key, NS, Ljung, LR, Manco‐Johnson, MJ, van Den Berg, HM, Srivastava, A, for the Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2014; 12: 1935– 9.

  • 4

    Belletrutti M, et al. (2020). Immune tolerance induction using wilate, a human von Willebrand factor/factor VIII complex, in patients with severe haemophilia A and inhibitors: A retrospective study of 11 children in two Canadian haemophilia treatment centres. Manuscript in preparation

  • 5

    Valentino, L.A., Kempton, C.L., Kruse‐Jarres, R., Mathew, P., Meeks, S.L., Reiss, U.M. and (2015), US Guidelines for immune tolerance induction in patients with haemophilia a and inhibitors. Haemophilia, 21: 559-567. doi:10.1111/hae.12730

  • 6

    Oldenburg, J., Jiménez‐Yuste, V., Peiró‐Jordán, R., Aledort, L.M. and Santagostino, E. (2014), Primary and rescue immune tolerance induction in children and adults: a multicentre international study with a VWF ‐containing plasma‐derived FVIII complex. Haemophilia, 20: 83-91. doi:10.1111/hae.12263

  • 7

    Gringeri A, Musso R, Mazzucconi MG et al. Immune tolerance induction with a high purity von Willebrand factor/VIII complex in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia 2007; 13: 373–9.

  • 8

    Kurth, M., Puetz, J., Kouides, P., Sanders, J., Sexauer, C., Bernstein, J., Gruppo, R., Manco-Johnson, M., Neufeld, E.J., Rodriguez, N., Wicklund, B., Quon, D. and Aledort, L. (2011), The use of a single von Willebrand factor‐containing, plasma‐derived FVIII product in hemophilia A immune tolerance induction: the US experience. Journal of Thrombosis and Haemostasis, 9: 2229-2234. doi:10.1111/j.1538-7836.2011.04493.x

  • 9

    Recommendation on the use and management of emicizumab-kxwh (Hemlibra) for hemophilia A with and without inhibitors. Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation (NHF) on November 21, 2018; adopted by the NHF Board of Directors on December 6, 2018. MASAC Document 255.

  • 10

    wilate® Full Prescribing Information. Paramus, NJ: Octapharma; rev November 2024.

Indications and Important Safety Information for wilate® [von Willebrand Factor/Coagulation Factor VIII Complex (Human)].

Please see wilate® full Prescribing Information.

Indication

wilate® is a von Willebrand Factor/Coagulation Factor VIII Complex (Human) indicated in children and adults with von Willebrand disease for 
on-demand treatment and control of bleeding episodes; for perioperative management of bleeding; and for routine prophylaxis to reduce the frequency of bleeding episodes in children 6 years of age and older and adults with VWD. wilate® is also indicated in adolescents and adults with hemophilia A for routine prophylaxis to reduce the frequency of bleeding episodes; and for on-demand treatment and control of bleeding episodes.

Contraindications

wilate® is contraindicated in patients with known hypersensitivity reactions, including anaphylactic or severe systemic reactions, to human plasma-derived products, any ingredient in the formulation, or components of the container.

Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions may occur with wilate®. Signs and symptoms include angioedema, burning and stinging at the infusion site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting, and wheezing that may progress to severe anaphylaxis (including shock) with or without fever. Closely monitor patients receiving wilate® and observe for any symptoms throughout the infusion period.

Because inhibitor antibodies may occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.

Thromboembolic Events

In VWD, continued treatment using a FVIII-containing VWF product may cause an excessive rise in FVIII activity, which may increase the risk of thromboembolic events. Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate® to avoid sustained excessive VWF and FVIII activity levels.

Neutralizing Antibodies

VWD

  • Neutralizing antibodies (inhibitors) to FVIII and VWF in patients with VWD, especially type 3 patients, may occur. If a patient develops inhibitor to VWF (or to FVIII), the condition will manifest itself as an inadequate clinical response. Thus, if expected VWF activity plasma levels are not attained, or if bleeding is not controlled with an adequate dose or repeated dosing, perform an appropriate assay to determine whether a VWF inhibitor is present.
  • In patients with antibodies against VWF, VWF is not effective and wilate® administration may lead to severe adverse events. Consider other therapeutic options for such patients.

Hemophilia A

  • Monitor plasma Factor VIII activity by performing a validated test (e.g., one stage clotting assay), to confirm that adequate Factor VIII levels have been achieved and maintained.
  • Monitor for the development of Factor VIII inhibitors. Perform a Bethesda inhibitor assay if expected Factor VIII plasma levels are not attained, or if bleeding is not controlled with the expected dose of wilate®. Use Bethesda Units (BU) to report inhibitor levels.

Transmissible Infectious Agents

wilate® is made from human plasma. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the variant Creutzfeldt-Jakob disease (vCJD) agent. There is also the possibility that unknown infectious agents may be present in the product. The risk that wilate® will transmit viruses has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and removing certain viruses during manufacture. Despite these measures, it may still potentially transmit disease.

Record the batch number of the product every time wilate® is administered to a patient, and consider appropriate vaccination (against hepatitis A and B virus) of patients in regular/repeated receipt of wilate®. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Octapharma USA, Inc., at 1-866-766-4860.

Monitoring and Laboratory Tests

  • Monitor plasma levels of VWF:RCo and FVIII activities in patients receiving wilate® to avoid sustained excessive VWF and FVIII activity levels, which may increase the risk of thromboembolism, particularly in patients with known clinical or laboratory risk factors.
  • Monitor for development of VWF and FVIII inhibitors. Perform assays to determine whether VWF and/or FVIII inhibitor(s) is present if bleeding is not controlled with the expected dose of wilate®.

Adverse Reactions

The most common adverse reactions to treatment with wilate® (≥ 1%) in patients with VWD were hypersensitivity reactions, urticaria, chest discomfort and dizziness. The most common adverse reactions to treatment with wilate® (≥ 1%) in previously treated patients with hemophilia A was pyrexia (fever).

Please see wilate® full Prescribing Information.

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FOR U.S. HEALTHCARE PROFESSIONALS ONLY

The information on this website has been specifically created 
for U.S. healthcare professionals (HCPs)

Please see wilate® full Prescribing Information

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© 2025 Octapharma USA, Inc. All rights reserved WIL-0678.