Hemophilia

Humate-P^®, Alphanate^®, and Wilate^® are complexes of antihemophilic factor VIII (FVIII) and von Willebrand factor (VWF) (human) indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A and the management of bleeding during surgical procedures in patients with von Willebrand disease (VWD) when the use of desmopressin is not recommended.^1-3 Humate-P is not recommended for prophylactic use in VWD.¹

Initial US Food and Drug Administration (FDA) approvals occurred in 1986, 1978, and 2009 for Humate-P, Alphanate, and Wilate, respectively.^1-3

Read more about von Willebrand disease.

FVIII/VWF Complex Mechanism of Action

Von Willebrand factor and FVIII are glycoproteins with important roles in hemostasis. Factor VIII deficiency is responsible for the development of hemophilia A, while deficient or absent VWF leads to VWD.⁴ Von Willebrand factor is an acute phase protein that allows platelets to anchor to the subendothelial matrix of damaged vessels while also protecting FVIII from proteolytic degradation.^4,5 Decreased VWF in the circulation leads to a decrease in FVIII and deficient platelet function.³ Factor VIII binds to VWF and, once activated, forms the tenase complex with factor IX, which is essential for the activation of factor X and the generation of thrombin and fibrin. Von Willebrand factor and FVIII circulate in the plasma and form the complex, FVIII/VWF. By infusing this complex into patients, the missing FVIII and VWF are temporarily replaced.^1-3

FVIII/VWF Complex Usage, Warnings, and Precautions

The FVIII/VWF complex is formulated as a purified, sterile, and lyophilized concentrate for intravenous administration and is available in single-dose vials. Its use is contraindicated in patients who have experienced hypersensitivity reactions to the product or any of its components.^1-3

The administration of FVIII/VWF complex may lead to the development of neutralizing antibodies and thromboembolic events. This complex is prepared from pooled human plasma, and therefore its administration carries a risk of transmission of infectious agents.^1-3

Get full prescribing information for HUMATE-P at MPR

FVIII/VWF Complex Efficacy and Safety 

Different studies for evaluating the efficacy and safety of the FVIII/VWF complex have been performed. The safety and efficacy of Humate-P was evaluated in patients with VWD undergoing surgery through 2 prospective, open-label, non-controlled, multicenter clinical studies. One of the studies was performed in the United States and focused on assessing the efficacy of Humate-P in the prevention of bleeding in adult and pediatric patients. Thirty-five patients were enrolled in the study, and 15 received a loading dose of Humate-P. The other 20 participants received a dose that was determined based on their individual pharmacokinetics for either major or minor surgery. All participants received maintenance doses. The second study, performed in Europe, evaluated the efficacy of Humate-P in correcting the coagulation defect in patients undergoing elective surgery. The dose of Humate-P administered to these participants was determined based on pharmacokinetic parameters obtained prior to surgery. The efficacy of Humate-P in both studies was evaluated immediately after surgery, 24 hours after the last administration, and 14 days after surgery. The results of both trials revealed that Humate-P was effective in preventing excessive bleeding during and after surgery.¹

The most frequent adverse reactions to Humate-P include allergic reactions such as urticaria, chest tightness, rash, pruritus, edema, injection-site bleeding, and epistaxis.¹

The efficacy of Alphanate in preventing excessive bleeding in patients with VWD undergoing surgery or invasive procedures was assessed in a retrospective, multicenter study.⁶ Sixty-one procedures performed in 39 participants were examined. The results reported that 93.5% of the responses to Alphanate treatment were classified as “excellent” or “good” by the investigators.⁶

Adverse reactions to Alphanate include pruritus, headache, rash, and chills.²

The efficacy of Wilate in controlling bleeding episodes in individuals with VWD was determined in 4 prospective, open-label, non-controlled clinical studies. Seventy participants aged 5 to 77 years were enrolled. The number of exposure days to Wilate ranged from 202 to 4917 days. Successful treatment of bleeding was achieved in 84% of bleeding episodes. A different study was performed in 28 participants with VWD undergoing 30 surgeries. The overall efficacy of Wilate for surgical procedures in this study was 96.7%. The use of Wilate for prophylaxis in hemophilia A was also evaluated in a prospective, open-label, multicenter study that included 55 adult and pediatric participants. The duration of prophylactic treatment with Wilate was 6 months. Data from this study showed that 54.6% of participants had 0 bleeding episodes, 21.8% of participants had 1 bleeding episode, 7.3% of participants had 2 bleeding episodes, 7.3% of participants had 3 bleeding episodes, and 9% of participants had 5 or more bleeding episodes.³

The most common adverse reactions to Wilate were hypersensitivity reactions, urticaria, ​​tightness of the chest, wheezing, hypotension, anaphylaxis, and dizziness in the trials with VWD patients and fever in the studies with hemophilia A patients.³

References

1. Humate-P. Prescribing information. CSL Behring; 2020. Accessed December 24, 2021.

2. Alphanate. Prescribing information. Grifols Biologicals LLC; 2021. Accessed December 24, 2021.

3. Wilate. Prescribing information. Octopharma; 2020. Accessed December 24, 2021.

4. Kiouptsi K, Reinhardt C. Physiological roles of the von Willebrand factor-factor VIII interaction. Subcell Biochem. 2020;94:437-464. doi:10.1007/978-3-030-41769-7_18

5. Federici AB. The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003;88(6):EREP02

6. Rivard GE, Aledort L; Alphanate Surgical Investigators. Efficacy of factor VIII/von Willebrand factor concentrate Alphanate in preventing excessive bleeding during surgery in subjects with von Willebrand disease. Haemophilia. 2008;14(2):271-275. doi:10.1111/j.1365-2516.2007.01616.x

Reviewed by Debjyoti Talukdar, MD, on 12/31/2021.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.