The diagnostic evaluation in cases of suspected hemophilia typically begins with a thorough review of the patient's personal bleeding history and family history. Screening tests are then performed and the diagnosis is confirmed with a specific clotting factor activity measurement(s) and/or genetic testing.
Diagnosis is made through family history, prothrombin time (PT) test, partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) test. Both the PT and aPTT would be prolonged in factor X deficiency. Diagnosis can be confirmed by a FX assay. Factor X deficiency is associated with bleeding in individuals who have a factor X activity level <10 percent (0.10 international units/mL).

In October 2015, the U.S. FDA approved Coagadex®, a coagulation Factor X (Human) product. Prior to this product becoming available, fresh-frozen plasma (FPP) or plasma-derived prothrombin complex concentrates (PCCs) were the only options for treatment of bleeds. However, the amount of FX varies between PCCs and treatment with PCCs should be used cautiously because at higher volumes they can produce blood clots. Coagadex®, a plasma derived concentrate, is indicated for individuals (aged 12 and older) with hereditary Factor X deficiency for on-demand treatment and control of bleeding episodes, and for the peri-operative management of bleeding in patients with mild and moderate hereditary Factor X deficiency.

In September 2018, the FDA approved Coagadex® for routine prophylaxis to reduce the frequency of bleed episodes.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

I. When anti-hemophilia products are considered medically necessary, initial therapy will be approved based on the following:

1. The provider must provide the actual prescribed dose with ALL of the following supporting documentation:
a. Patient’s age
b. Patient’s weight
c. Severity of the factor deficiency
i. (i.e., severe = <1% factor activity, moderate = ≥1 to ≤5% factor activity, mild = >5 to 40% factory activity)
d. Bleed history
e. Inhibitor status
f. Intended use/regimen: prophylaxis, on-demand, peri-operative

1. Hereditary Factor X deficiency
· Diagnosis of congenital factor X deficiency has been confirmed by blood coagulation testing; AND
· Used for on-demand treatment and control of bleeding episodes; OR
· Used for routine prophylaxis to reduce the frequency of bleeding episodes; OR
· Member must meet either of the following criteria:
· Severe factor X deficiency (factor X level of <1%); or
· At least two documented episodes of spontaneous bleeding into joints
· Used for perioperative management of surgical bleeding in patients with mild and moderate deficiency
· Limitation of use: perioperative management of bleeding in major surgery in patients with severe hereditary Factor X deficiency has not been studied
· For members with a BMI ≥ 30, a half-life study should be performed to determine the appropriate dose and dosing interval.
· For minimally treated patients (< 50 exposure days to factor products) previously receiving a different factor product, inhibitor testing is required at baseline in any patient that has received factor, then at every comprehensive care visit (yearly for the mild and moderate patients, semi-annually for the severe patients).

1. Initial authorization period varies by specific indication:
a. On-demand treatment and control of bleeding episodes
o Unless otherwise specified, the initial authorization for acute treatment will be 6 months and may be renewed.
· The cumulative amount of medication(s) the patient has on-hand will be taken into account when authorizing. The authorization will allow up to 5 doses on-hand for the treatment of acute bleeding episodes as needed for the duration of the authorization.
b. Perioperative management of surgical bleeding in patients with mild and moderate deficiency
o Unless otherwise specified, the authorization is valid for 1 month
c. Routine prophylaxis to reduce the frequency of bleeding episodes
o Unless otherwise specified, the initial authorization for prophylaxis treatment will be 12 months and may be renewed.
2. For patients whom PK test is recommended, initial approval will be for 3 months and renewal will be based upon completion of the PK test.

[INFORMATIONAL NOTE: Requirements for half-life study are a part of the hemophilia management program. This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide. ]

3. Dispensing Requirements for Renderings Providers
a. Prescriptions cannot be filled without an expressed need from the patient, caregiver or prescribing practitioner. Auto-filling is not allowed.
b. Monthly, rendering provider must submit for authorization of dispensing quantity before delivering factor product. Information submitted must include:
· Original prescription information, requested amount to be dispensed and patient clinical history (including patient product inventory and bleed history)
· Factor dose should not exceed +1% of the prescribed dose and a maximum of three vials may be dispensed per dose. If unable to provide factor dosing within required range of prescribed dose, then rendering provider must provide proof of all available vial sizes from the manufacturer prior to dispensing factor product and the lowest possible dose able to be achieved above +1% should be dispensed. Prescribed dose should not be increased to meet assay management requirements.
c. The prescriber should discuss with the patient that a treatment log should be maintained and a copy should be submitted (via prescriber or pharmacy) upon request for renewal purposes.

· Patient continues to meet criteria identified in section I and II and dosing identified in section III; AND
· Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following:
· Symptoms of allergic-anaphylactic reactions (anaphylaxis, dyspnea, rash);
· Development of neutralizing antibodies (inhibitors); AND
o To determine if factor X inhibitors are present, perform a Bethesda assay. The presence of inhibitors should be suspected if the expected factor X activity concentration in plasma is not attained or if bleeding is not controlled with the recommended dose. Monitor all patients regularly for the development of inhibitors by appropriate clinical observations and laboratory tests.
· Any increases in dose must be supported by an acceptable clinical rationale (i.e. weight gain, half-life study results, increase in breakthrough bleeding when patient is fully adherent to therapy, etc.).
· Monitor plasma factor X activity by performing the one-stage clotting assay to confirm adequate concentrations of factor X have been achieved and maintained. .
· The cumulative amount of medication (s) the patient has on-hand will be taken into account when authorizing. The authorization will allow up to 5 doses on-hand for the treatment of acute bleeding episodes as needed for duration of the authorization.
· For the following disease specific criteria, renewal will be approved for a 6 month authorization period:
· Treatment of acute bleeding episodes
· Treatment of spontaneous and trauma-induced bleeding episodes
· On-demand treatment of bleeding episodes
· For the following disease specific criteria, renewal will be approved for a 12 month authorization period:
· Routine prophylaxis to prevent or reduce the frequency of bleeding episodes
· Prevention of acute bleeding episodes
· Dispensing Requirements for Renderings Providers
a. Prescriptions cannot be filled without an expressed need from the patient, caregiver or prescribing practitioner. Auto-filling is not allowed.
b. Monthly, rendering provider must submit for authorization of dispensing quantity before delivering factor product. Information submitted must include:
· Original prescription information, requested amount to be dispensed and patient clinical history (including patient product inventory and bleed history)
· Factor dose should not exceed +1% of the prescribed dose and a maximum of three vials may be dispensed per dose. If unable to provide factor dosing within required range of prescribed dose, then rendering provider must provide proof of all available vial sizes from the manufacturer prior to dispensing factor product and the lowest possible dose able to be achieved above +1% should be dispensed. Prescribed dose should not be increased to meet assay management requirements.
c. The prescriber should discuss with the patient that a treatment log should be maintained and a copy should be submitted (via prescriber or pharmacy) upon request for renewal purposes.

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Hemophilia Products - Factor X: Coagadex
Coagadex
Factor X

References:
1. Coagadex [package insert]. Durham, NC; Bio Products Laboratory; September 2018

2. MASAC RECOMMENDATIONS CONCERNING PRODUCTS LICENSED FOR THE TREATMENT OF HEMOPHILIA AND OTHER BLEEDING DISORDERS. 2013 National Hemophilia Foundation. MASAC Document #240; February 2016. Available at: http://www.hemophilia.org. Accessed June 2016.

3. First Coast Service Options, Inc. Local Coverage Determination (LCD): Hemophilia Clotting Factors (L33684). Centers for Medicare & Medicaid Services, Inc. Updated on 01/21/2016 with effective date 01/01/2016. Accessed February 2016.

4. Novitas Solutions, Inc. Local Coverage Determination (LCD): Hemophilia Clotting Factors (L35111). Centers for Medicare & Medicaid Services, Inc. Updated on 01/22/2016 with effective date 01/01/2016. Accessed February 2016.

5. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Access June 2016.

6. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.

7. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.

8. Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2014; 12:1935.

9. Guidelines for the management of hemophilia, 2^nd edition. 2012 World Federation of Hemophilia. July 2012. Available at: https://www1.wfh.org/publication/files/pdf-1472.pdf. Accessed March 2018.

10. Chernecky CC, Berger BJ. Factor X (Stuart-Prower factor) - blood. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures. 6th ed. St Louis, MO: Elsevier Saunders; 2013:506-507.

11. Gailani D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 139.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*