Coverage Policy Manual
Policy #: 2024062
Category: Pharmacy
Initiated: January 2025
Last Review: September 2025
  Factor IX (e.g., AlphaNine, Alprolix, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Rebinyn, Rixubis)
Description:
Factor IX is a vitamin K-dependent clotting factor that is synthesized in the liver. In individuals with hemophilia B there is a deficiency in functional coagulation factor IX leading to a prolonged clotting time in the activated partial thromboplastin time (aPTT) assay. The administration of factor IX replacement to deficient individuals results in increased levels of factor IX thereby decreasing the risk of hemorrhage or restoring hemostasis.
 
Both plasma-derived (AlphaNine, Mononine, Profilnine) and recombinant (BeneFIX, Ixinity, Rixubis, Idelvion, Rebinyn, Alprolix) concentrates are suitable for hemophilia B management; however, due to their better safety profile, recombinant factor IX products are often the first choice of treatment in industrialized countries.
 
Products containing only factor IX tend to be preferable to complex concentrates. AlphaNine SD, Mononine and Profilnine also contain factors II, VII, IX, and X which may increase the risk of thromboembolism.
 
The development of factor IX products with prolonged half-lives improves individual adherence by enabling less frequent infusions, decreasing the bleeding rate, and reducing the burden of treatment. Several technologies have been applied to extend the half-life of factor IX, such as Factor IX Fc fusion protein (Alprolix), which contains the Fc region of human IgG1, which binds to the neonatal Fc receptor (FcRn). FcRn is part of a naturally occurring pathway that delays lysosomal degradation of immunoglobulins by cycling them back into circulation and prolonging their plasma half-life. The genetic fusion of recombinant albumin to recombinant factor IX, as seen with Idelvion, also extends the half-life of factor IX. The factor IX in Rebinyn is conjugated to a 40-kDa polyethylene glycol molecule, which slows down its removal from the blood circulation.
 
Regulatory Status
 
Coagulation factor IX, recombinant (e.g., Ixinity) was approved by the U.S. Food and Drug Administration (FDA) on April 30, 2015, for bleeding prophylaxis and treatment in adults and children over age of 12 with Hemophilia B. On March 26, 2024, FDA expanded Ixinity approval to pediatric individuals under 12 years of age with Hemophilia B.
 
Coagulation factor IX, recombinant glycoPEGylated (e.g., Rebinyn) was approved by the U.S. Food and Drug Administration (FDA) on May 31, 2017, for on-demand treatment and control of bleeding episodes, and the perioperative management of bleeding in adults and children with hemophilia B. On July 29, 2022, FDA expanded Rebinyn approval to routine prophylaxis in individuals with Hemophilia B.
 
Coagulation factor IX, recombinant albumin fusion protein (e.g., Idelvion) was approved by the U.S. Food and Drug Administration (FDA) on March 4, 2016, for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coagulation factor IX, recombinant Fc fusion protein (e.g., Alprolix) was approved by the U.S. Food and Drug Administration (FDA) on March 28, 2014, for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coagulation factor IX, recombinant (e.g., Rixubis) was approved by the U.S. Food and Drug Administration (FDA) on June 27, 2013, for bleeding prophylaxis and treatment in individuals with Hemophilia B who are 16 years of age and older.
 
Coagulation factor IX, recombinant (e.g., BeneFIX) was approved by the U.S. Food and Drug Administration (FDA) in 1997 for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coagulation factor IX, human (e.g., AlphaNine) was approved by the U.S. Food and Drug Administration (FDA) in 1996, for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coagulation factor IX, human (e.g., MonoNine) was approved by the U.S. Food and Drug Administration (FDA) in 1992, for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coagulation factor IX, human (e.g., Profilnine) was approved by the U.S. Food and Drug Administration (FDA) in 1986, for bleeding prophylaxis and treatment in adults and children with Hemophilia B.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
This policy addresses the use of the intravenous Factor IX in the outpatient setting only. This policy does not apply to the use of factor IX in inpatient or emergency room settings.
 
INITIAL AND CONTINUATION APPROVAL will be for duration of treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective September 2025  
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Factor IX (e.g., AlphaNine, Alprolix, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Rebinyn, Rixubis) 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 B
 
INITIAL APPROVAL:
 
1. Individual has a diagnosis of severe hemophilia B (see policy guidelines); AND individual is using for one of the following:
a. Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; OR
b. On-demand treatment and control of bleeding episodes; OR
c. Peri-procedural management for surgical, invasive, or interventional radiology procedures; OR
2. Individual has a diagnosis of mild to moderate hemophilia B (see policy guidelines); AND individual is using for one of the following:
a. On-demand treatment and control of bleeding episodes; OR
b. Peri-procedural management for surgical, invasive, or interventional radiology procedures; OR
3. Individual has diagnosis of mild to moderate hemophilia B (see policy guidelines) with intention to use factor IX as routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes AND one of the following criteria is met (NHF, Srivastava 2020):
a. One or more episodes of spontaneous bleeding into joint; OR
b. One or more episodes of spontaneous bleeding into the central nervous system; OR
c. Four or more episodes of soft tissue bleeding in an 8-week period; OR
d. Individual’s risk factors increase the risk of a clinically significant bleed, including but not limited to, participation in activities likely to cause injury/trauma, procoagulant and anticoagulant protein levels, comorbid conditions affecting functional ability and physical coordination, or history of a clinically significant bleed; AND
4. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist.
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
IMMUNE TOLERANCE INDUCTION
 
INITIAL APPROVAL:
 
1. Individual has a diagnosis of hemophilia B; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. Individual is using for immune tolerance therapy.
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
FACTOR II DEFICIENCY
 
INITIAL APPROVAL:
 
1. Individual has a diagnosis of factor II deficiency; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. The prescribed product is Profilnine.
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
FACTOR X DEFICIENCY
 
INITIAL APPROVAL:
 
1. Individual has a diagnosis of factor X deficiency; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. The prescribed product is Profilnine.
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) 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 IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
DOSAGE AND ADMINISTRATION
 
For FDA labeled indications, Factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.
 
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.
 
The recommended dose of factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) is calculated by multiplying individual’s body weight and the percent of desired increase in plasma factor IX, resulting in the number of factor IX international units required.
 
Factor IX (e.g., AlphaNine) is available as 500-unit vials, 1000-unit vials and 1500-unit vials.
 
Factor IX (e.g., Alprolix) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials, 3000-unit vials and 4000-unit vials.
 
Factor IX (e.g., BeneFIX) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Idelvion) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3500-unit vials.
 
Factor IX (e.g., Ixinity) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Mononine) is available as a 1000-unit vial.
 
Factor IX (e.g., Profilnine) is available as 500-unit vials, 1000-unit vials and 1500-unit vials.
 
Factor IX (e.g., Rebinyn) is available as 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Rixubis) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) should be administered as an intravenous 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.
 
Effective January 1, 2025  to August 2025
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Factor IX (e.g., AlphaNine, Alprolix, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Rebinyn, Rixubis) 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 B
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual has a diagnosis of severe hemophilia B (see policy guidelines); AND individual is using for one of the following:
a. Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; OR
b. On-demand treatment and control of bleeding episodes; OR
c. Peri-procedural management for surgical, invasive, or interventional radiology procedures; OR
2. Individual has a diagnosis of mild to moderate hemophilia B (see policy guidelines); AND individual is using for one of the following:
a. On-demand treatment and control of bleeding episodes; OR
b. Peri-procedural management for surgical, invasive, or interventional radiology procedures; OR
3. Individual has diagnosis of mild to moderate hemophilia B (see policy guidelines) with intention to use factor IX as routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes AND one of the following criteria is met (NHF, Srivastava 2020):
a. One or more episodes of spontaneous bleeding into joint; OR
b. One or more episodes of spontaneous bleeding into the central nervous system; OR
c. Four or more episodes of soft tissue bleeding in an 8-week period; OR
d. Individual’s risk factors increase the risk of a clinically significant bleed, including but not limited to, participation in activities likely to cause injury/trauma, procoagulant and anticoagulant protein levels, comorbid conditions affecting functional ability and physical coordination, or history of a clinically significant bleed; AND
4. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist.
 
CONTINUED APPROVAL for up to 12 months:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
IMMUNE TOLERANCE INDUCTION
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual has a diagnosis of hemophilia B; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. Individual is using for immune tolerance therapy.
 
CONTINUED APPROVAL for up to 12 months:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
FACTOR II DEFICIENCY
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual has a diagnosis of factor II deficiency; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. The prescribed product is Profilnine.
 
CONTINUED APPROVAL for up to 12 months:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
FACTOR X DEFICIENCY
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
1. Individual has a diagnosis of factor X deficiency; AND
2. Factor IX replacement is prescribed by or in consultation with a hemophilia specialist; AND
3. The prescribed product is Profilnine.
 
CONTINUED APPROVAL for up to 12 months:
 
1. Individual continues to meet initial approval criteria; AND
2. Individual experienced clinical improvement while on factor IX therapy (e.g., decreased frequency or severity of bleeds).
 
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.
 
The recommended dose of factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) is calculated by multiplying individual’s body weight and the percent of desired increase in plasma factor IX, resulting in the number of factor IX international units required.
 
Factor IX (e.g., AlphaNine) is available as 500-unit vials, 1000-unit vials and 1500-unit vials.
 
Factor IX (e.g., Alprolix) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials, 3000-unit vials and 4000-unit vials.
 
Factor IX (e.g., BeneFIX) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Idelvion) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3500-unit vials.
 
Factor IX (e.g., Ixinity) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Mononine) is available as a 1000-unit vial.
 
Factor IX (e.g., Profilnine) is available as 500-unit vials, 1000-unit vials and 1500-unit vials.
 
Factor IX (e.g., Rebinyn) is available as 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., Rixubis) is available as 250-unit vials, 500-unit vials, 1000-unit vials, 2000-unit vials and 3000-unit vials.
 
Factor IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) should be administered as an intravenous 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 IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis) 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 IX (e.g., AlphaNine, Alprolix, Bebulin, BeneFIX, Idelvion, Ixinity, Mononine, Profilnine, Proplex, Rebinyn, Rixubis), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
Guidelines for hemophilia from the National Bleeding Disorders Foundation (2023) and the World Federation of Hemophilia (2020) recognize the important role of Factor IX products in the management of hemophilia B individuals. Individuals with mild hemophilia B may only experience abnormal bleeding during surgery, during tooth extractions, or when injured. Individuals with moderate hemophilia B generally have prolonged bleeding responses to minor trauma. Severe hemophilia B is marked by spontaneous bleeding such as spontaneous hemarthrosis, soft-tissue hematomas, retroperitoneal bleeding, intracerebral hemorrhage, and delayed bleeding post-surgery. Complications from recurrent bleeding and soft-tissue hematomas include severe arthropathy, and joint contractures, which may lead to pain and disability. The main treatment of hemophilia B is replacement of missing blood coagulation factor with Factor IX products. Factor IX replacement therapy may be used on-demand when bleeding occurs or given as routine prophylaxis with scheduled infusions. Both plasma-derived and recombinant Factor IX products are available. In general, prophylactic therapy has been associated with a reduction in bleeds and improved outcomes for selected individuals (e.g., individuals with moderate or severe factor IX deficiency). The goal of therapy is to prevent uncontrolled internal hemorrhage and severe joint damage, and to effectively manage bleeding episodes. The development of inhibitors occurs at a lower frequency in individuals with severe hemophilia B compared with severe hemophilia A but can occur in up to 5% of individuals. Higher doses than those are typically used for the uses of standard half-life products can be given if the individual develops an inhibitor.
 
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2025. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J7193Factor ix (antihemophilic factor, purified, non recombinant) per i.u.
J7194Factor ix, complex, per i.u.
J7195Injection, factor ix (antihemophilic factor, recombinant) per iu, not otherwise specified
J7200Injection, factor ix, (antihemophilic factor, recombinant), rixubis, per iu
J7201Injection, factor ix, fc fusion protein, (recombinant), alprolix, 1 i.u.
J7202Injection, factor ix, albumin fusion protein, (recombinant), idelvion, 1 i.u.
J7203Injection factor ix, (antihemophilic factor, recombinant), glycopegylated, (rebinyn), 1 iu
J7213Injection, coagulation factor ix (recombinant), ixinity, 1 i.u.
References: AlphaNine(2022) Package insert Los Angeles, CA: Grifols Biologicals.

Alprolix intravenous infusion(2023) prescribing information Waltham, MA: Bioverativ/Sanofi; May 2023.

BeneFIX(2022) Package insert Philadelphia, PA: Wyeth Pharmaceuticals.

Croteau SE.(2022) Hemophilia A/B. Hematol Oncol Clin N Am. 2022; 36:797-812.

Idelvion intravenous infusion(2023) prescribing information Kankakee, IL: CSL Behring; June 2023.

Ixinity intravenous infusion(2022) prescribing information Chicago, IL: Medexus; November 2022.

Mancuso ME, Mahlangu JN, Pipe SW.(2021) The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing. Lancet. 2021; 397:630-640.

Menegatti M, Peyvandi F.(2019) Treatment of rare factor deficiencies other than hemophilia. Blood. 2019;133(5):415-424.

MonoNine(2018) Package insert Kankakee, IL: CSL Behring.

National Bleeding Disorders Foundation.(2023) MASAC recommendations concerning products licensed for the treatment of hemophilia selected disorders of the coagulation system (Revised August 19, 2023, and endorsed on August 20, 2023). Available at: https://www.hemophilia.org/sites/default/files/document/files/MASAC-Products-Licensed.pdf. Accessed on July 7, 2024.

Profilnine(2010) Package insert Los Angeles, CA: Grifols Biologicals.

Rebinyn intravenous infusion(2022) prescribing information Plainsboro, NJ: Novo Nordisk; August 2022.

Rixubis intravenous infusion(2023) prescribing information Lexington, MA: Baxalta/Takeda; March 2023.

Sidonio RF, Malec L.(2021) Hemophilia B (Factor IX Deficiency). Hematol Oncol Clin North Am. 2021;35(6):1143-1155.

Srivastava A, Santagostino E, Dougall A, on behalf of the WFH guidelines for the management of hemophilia panelists and co-authors.(2020) Guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1-158.

Tepezza(2023) package insert Deerfield, IL: Horizon Therapeutics.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
CPT Codes Copyright © 2025 American Medical Association.