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Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Wilate, Xyntha) | |
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Description: |
Clotting factors and coagulant blood products are used in various bleeding and coagulation disorders. Coagulation disorders cause dysfunction of hemostasis. Coagulation disorders can be acquired or hereditary. Acquired coagulation disorders can be caused by liver disease, vitamin K deficiency, development of circulating anticoagulants or other causes. Hereditary coagulation disorders, such as hemophilia, are due to a genetic deficiency of a factor or component of the coagulation cascade required for hemostasis. Acquired and hereditary coagulation disorders are both generally treated with factor replacement using either recombinant or plasma-derived products, though new novel therapies are currently available with more in-development.
This document will address the use of the following anti-hemophilic clotting factor VIII products for hemophilia A:
Hemophilia A or classic hemophilia is a deficiency of factor VIII. Factor VIII, or antihemophilic factor, is an endogenous glycoprotein necessary for blood clotting and hemostasis. It is a cofactor necessary for factor IX to activate factor X in the intrinsic pathway. Per the National Hemophilia Foundation (NHF), hemophilia occurs in 1 in 5,000 live births in the United States and hemophilia A is 4 times more common than hemophilia B. (NHF, 2016) The average normal plasma activity of factor VIII is designated as 100%, and a factor VIII concentration of 25% of normal is required for hemostasis. Individuals with severe hemophilia have a factor VIII concentration of less than 1% of normal and frequently experience bleeding even in the absence of trauma. Individuals with a factor VIII concentration between 1% and 5% (moderate hemophilia) experience less bleeding, and individuals with a factor VIII concentration greater than 5% (mild hemophilia) usually experience bleeding only after obvious trauma. The administration of factor VIII temporarily replaces the missing clotting factor to correct or prevent bleeding episodes. Factor VIII is obtained from pooled human plasma or produced by recombinant deoxyribonucleic acid (DNA) technology. Three products contain factor VIII and von Willebrand factor (Alphanate, Humate-P, and Koate), but only Alphanate and Humate-P have the indication for the treatment of von Willebrand disease.
Regulatory Status
Factor VIII antihemophilic factor, recombinant (e.g., Advate) was approved by the U.S. Food and Drug Administration (FDA) on July 25, 2003, for the treatment of Hemophilia A. Advate is not indicated for the treatment of von Willebrand disease.
Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) was approved by the U.S. Food and Drug Administration (FDA) on November 13, 2015, for the treatment of Hemophilia A. On December 27, 2016, FDA has extended approved use to children and surgical settings. Adynovate is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation recombinant single chain (e.g., Afstyla) was approved by the U.S. Food and Drug Administration (FDA) on May 26, 2016, for the treatment of Hemophilia A. Afstyla is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) was approved by the U.S. Food and Drug Administration (FDA) on August 15, 1978, for the treatment of Hemophilia A. Alphanate is also indicated for surgical and/or invasive procedures in adult and pediatric individuals with von Willebrand Disease (VWD) in whom desmopressin (DDAVP) is either ineffective or contraindicated. It is not indicated for individuals with severe VWD (Type 3) undergoing major surgery.
Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) was approved by the U.S. Food and Drug Administration (FDA) on February 22, 2023, for the treatment of Hemophilia A. On May 10, 2024, FDA has extended approved use to children. Altuviiio is not indicated for the treatment of von Willebrand disease.
Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) was approved by the U.S. Food and Drug Administration (FDA) on June 6, 2024, for the treatment of Hemophilia A. Eloctate is not indicated for the treatment of von Willebrand disease.
Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) was approved by the U.S. Food and Drug Administration (FDA) on February 19, 2019, for the treatment of Hemophilia A. Esperoct is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor (human) (e.g., Hemofil-M) was approved by the U.S. Food and Drug Administration (FDA) on March 11, 1966, for the treatment of Hemophilia A. Hemofil- M is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) was approved by the U.S. Food and Drug Administration (FDA) in April 1986, for the treatment of Hemophilia A.
Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) was approved by the U.S. Food and Drug Administration (FDA) on August 30, 2018, for the treatment of Hemophilia A. Jivi is not indicated for use in children less than 12 year of age due to a greater risk of hypersensitivity reactions. Jivi is not indicated for use in previously untreated individuals and Jivi is not indicated for the treatment of von Willebrand disease.
Factor VIII antihemophilic factor (human) (e.g., Koate) was approved by the U.S. Food and Drug Administration (FDA) on January 24, 1974, for the treatment of Hemophilia A. Koate is not indicated for the treatment of von Willebrand disease.
Factor VIII octocog alfa (e.g., Kogenate FS) was approved by the U.S. Food and Drug Administration (FDA) on February 25, 1993, for the treatment of Hemophilia A. Kogenate is not indicated for the treatment of von Willebrand disease.
Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) was approved by the U.S. Food and Drug Administration (FDA) on March 16, 2016, for the treatment of Hemophilia A. Kovaltry is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor, recombinant (e.g., NovoEight) was approved by the U.S. Food and Drug Administration (FDA) on October 15, 2013, for the treatment of Hemophilia A. NovoEight is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) was approved by the U.S. Food and Drug Administration (FDA) on September 4, 2015, for the treatment of Hemophilia A. Nuwiq is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) was approved by the U.S. Food and Drug Administration (FDA) on October 23, 2014, for the treatment of adults with acquired hemophilia A. Obizur is not indicated for treatment of congenital hemophilia A or von Willebrand disease. Safety and efficacy of Obizur has not been established in individuals with baseline anti-porcine factor VIII inhibitor titer greater than 20 units.
Factor VIII coagulation factor, recombinant (e.g., Recombinate) was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1992, for the treatment of Hemophilia A. Recombinate is not indicated for the treatment of von Willebrand disease.
Factor VIII coagulation factor with von Willebrand factor (e.g., Wilate) was approved by the U. S. Food and Drug Administration (FDA) on December 8, 2009, for the treatment of von Willebrand disease. On August 13,2015 Wilate received approval for perioperative management and on October 8, 2019, Wilate was approved for Hemophilia A in adolescent and adult individuals. On December 7, 2023, Wilate was approved for prophylaxis in all types of von Willebrand disease.
Factor VIII coagulation factor, recombinant (e.g., Xyntha) was approved by the U.S. Food and Drug Administration (FDA) on February 21, 2008, for the treatment of Hemophilia A. Xyntha is not indicated for the treatment of von Willebrand disease.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
This policy addresses the use of the intravenous Factor VIII in the outpatient setting only. This policy does not apply to the use of factor VIII in inpatient or emergency room settings.
Effective Date January 1, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Wilate, Xyntha) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
HEMOPHILIA A
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
VON WILLEBRAND DISEASE PERI-PROCEDURAL ADMINISTRATION
INITIAL APPROVAL STANDARD REVIEW for up to 6 months:
NOTE: Pure Factor VIII replacement is not indicated for individuals with severe Von Willebrand Disease (Type 3) undergoing major surgery.
VON WILLEBRAND DISEASE ROUTINE PROPHYLAXIS
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
Policy Guidelines
Severe Hemophilia A is defined as less than 1% of normal endogenous factor VIII or less than 1 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Mild to moderate Hemophilia A is defined as greater than 1% but less than 40% of normal endogenous factor VIII or greater than 1 but less than 40 international unit per deciliter of blood of endogenous factor VIII (NHF, Srivastava, 2020).
Management of von Willebrand Disease:
Desmopressin (DDAVP) is recommended for the majority of type 1 individuals and for clinically responsive type 2A individuals. VWF-containing Factor VIII concentrates are recommended for type 1 and 2A individuals who become transiently unresponsive to DDAVP and in surgical situations and for type 2B and 3 VWD that do not respond to DDAVP. While not FDA-approved for VWD, Koate- is listed as possibly effective for some individuals (NHF, 2015).
The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of Hemofil M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight (Addiego et al, 1992).
Contraindications to desmopressin in Type 1, 2A, 2N and 2M disease:
There are two forms of von Willebrand disease, inherited and acquired. The inherited form is the most common and is divided into three major types:
VWD screening tests assess the quantity and function of VWF. The quantity of VWF is measured by VWF antigen (VWF:Ag), and the function (platelet dependent VWF activity) of VWF is measured by VWF:RCo (ristocetin cofactor) or VWF:GPIbM assays. VWF:Ag or VWF activity less than 30% confirms the diagnosis of VWD in individuals without bleeding history. VWF:Ag or VWF activity should be 30-50% in individuals with a positive bleeding history to confirm the diagnosis.
Dosage and Administration
Dosing per FDA Guidelines
Authorizations for routine prophylaxis will be given to allow for both prophylactic and doses required to be on hand in the event of acute bleed.
The dosing of clotting factor concentrates is highly individualized. MASAC provides recommendations regarding doses of clotting factor concentrate in the home (MASAC, 2016). The number of required doses varies greatly and is dependent on the severity of the disorder and the prescribed regimen. Per MASAC guidance, individuals on prophylaxis should also have at least one major dose and two minor doses on hand for breakthrough episodes and the prophylactic doses used monthly. The guidance also notes that an adequate supply of clotting factor concentrate is needed to accommodate weekends and holidays. Therefore, maximum doses in this policy allows for prophylactic dosing plus three days of acute episodes or perioperative management per 28 days. Doses exceeding this quantity will be reviewed on a case-by-case basis by a clinician.
A. The recommended dose of factor VIII antihemophilic factor, recombinant (e.g., Advate) is as follows:
B. The recommended dose of Factor VIII antihemophilic factor, recombinant PEGylated (e.g., Adynovate) is as follows:
C. The recommended dose of Factor VIII coagulation recombinant single chain (e.g., Afstyla) is as follows:
D. The recommended dose of Factor VIII coagulation factor with von Willebrand factor (e.g., Alphanate) is as follows:
E. The recommended dose of Factor VIII antihemophilic factor recombinant, Fc-VWF-XTEN fusion protein-ehtl (e.g., Altuviiio) is as follows:
F. The recommended dose of Factor VIII antihemophilic factor, Fc fusion protein (e.g., Eloctate) is as follows:
G. The recommended dose of Factor VIII antihemophilic factor, glycopegylated-exei (e.g., Esperoct) is as follows:
H. The recommended dose of Factor VIII coagulation factor (human) (e.g., Hemofil-M) is as follows:
I. The recommended dose of Factor VIII coagulation factor; von Willebrand factor (e.g., Humate-P) is as follows:
J. The recommended dose of Factor VIII antihemophilic factor, PEGylated-aucl (e.g., Jivi) is as follows:
K. The recommended dose of Factor VIII antihemophilic factor (human) (e.g., Koate) is as follows:
L The recommended dose of Factor VIII octocog alfa (e.g., Kogenate FS) is as follows:
M. The recommended dose of Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is as follows:
Factor VIII antihemophilic factor, recombinant (e.g., Kovaltry) is available as single-use vials containing nominally: 250, 500, 1000, 2000, or 3000 international units.
N. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., NovoEight) is as follows:
O. The recommended dose of Factor VIII coagulation factor, recombinant human (e.g., Nuwiq) is as follows:
P. The recommended dose of Factor VIII coagulation factor, recombinant porcine sequence (e.g., Obizur) is as follows:
Q. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Recombinate) is as follows:
R. The recommended dose of Factor VIII coagulation factor, recombinant (e.g., Xyntha) is as follows:
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha) should be administered as an IV infusion by a healthcare professional or a trained individual.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, factor VIII (e.g., Advate, Adynovate, Afstyla, Alphanate, Altuviiio, Eloctate, Esperoct, Jivi, Hemofil-M, Humate-P, Koate, Kogenate, Kovaltry, Novoeight, Nuwiq, Obizur, Recombinate, Xyntha), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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Rationale: |
The National Hemophilia Foundation (NHF) Medical and Scientific Advisory Council (MASAC) has recommendations concerning products used for the treatment of hemophilia and other bleeding disorders. It is noted that recombinant Factor VIII products are the recommended treatment of choice for individuals with hemophilia A. The MASAC recommendations regarding plasma-derived Factor VIII products state that improved viral-depleting processes and donor screening practices have greatly reduced the risk of transmission and human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C virus (MASAC, 2018).
In 2012 the American Society of Hematology (ASH) published a summary guide to the National Heart, Lung, and Blood Institute 2007 recommendations for managing von Willebrand disease. Desmopressin (DDAVP) and von Willebrand factor replacement products (Humate-P, Wilate, Koate, and Alphanate) are listed as therapies to elevate VWF. Some of the key management recommendations from the guide regarding treatment of minor and major bleeding and prophylaxis for minor and major surgery include:
The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation (NHF) includes recommendations for management of VWD. Most individuals with von Willebrand Disease type 1 may be treated witheither desmopressin (either parenterally [DDAVP injection] or by a highly concentrated nasal spray [Stimate nasal spray]). For surgery, trauma, or other serious bleeding episodes, if hemostasis is not achieved using DDAVP, a Factor VIII concentrate that contains high molecular weight multimers of vWF should be used. Individuals with type 2B and type 3 von Willebrand Disease, and those with type 1, 2A, 2M, and 2N who have not responded adequately to DDAVP should be treated with a Factor VIII concentrate that contains higher molecular weight multimers of vWF. Products FDA-approved for this use include Alphanate, Humate P, and Wilate. Koate may be effective but it not FDA-approved for this use. (MASAC, 2018)
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CPT/HCPCS: | |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association. |