Subject:
Hemophilia Products – von Willebrand Factor (von Willebrand Disease): Vonvendi
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Hemophilia is a rare disorder in which the blood does not clot normally. It is a medical condition in which the ability of the blood to clot is severely reduced, causing the sufferer to bleed severely from even a slight injury. The condition is typically caused by a hereditary lack of a coagulation factor, most often factor VIII. Differentiation between hemophilia and other conditions, such as some types of von Willebrand disease or acquired factor inhibitors, and distinction between hemophilia A and B are crucial for appropriate management.
Von Willebrand disease (VWD) is the most common type of bleeding disorder however it is generally less severe than other bleeding disorders. People with VWD have a problem with a protein in their blood called von Willebrand factor (VWF) that helps control bleeding. For most people with VWD, the disorder causes little or no disruption to their lives except when there is a serious injury or need for surgery. It is estimated that up to 1% of the world’s population suffers from VWD, but because many people have only very mild symptoms, only a small number of them know they have it.
Clinical manifestations relate to bleeding from impaired hemostasis, sequelae from bleeding, or complications of coagulation factor infusion. Patients often bleed in response to minor intercurrent injury and invasive procedures.
There are three main types of VWD. Within each type, the disorder can be mild, moderate, or severe. Bleeding symptoms can be quite variable within each type depending in part on the VWF activity.
1. Type 1 VWD is the most common form. People with Type 1 VWD have lower than normal levels of VWF. Symptoms are usually very mild. Still, it is possible for someone with Type 1 VWD to have serious bleeding.
2. Type 2 VWD involves a defect in the VWF structure. The VWF protein does not work properly, causing lower than normal VWF activity. Symptoms are usually moderate.
3. Type 3 VWD is usually the most serious form. People with Type 3 VWD have very little or no VWF. Symptoms are more severe. People with Type 3 VWD can have bleeding into muscles and joints, sometimes without injury.
The diagnostic evaluation in cases of suspected WVD 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. Initial testing includes screening tests of hemostasis, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count. Mixing studies for the aPTT assay are performed if the aPTT is prolonged. If mixing studies show correction, consistent with a factor deficiency rather than an inhibitor, factor activity levels are then measured. An exception is diagnosis in a male neonate with a positive family history, in which factor levels are often measured directly on cord blood.
Table 1: The 2nd edition World Federation of Hemophilia (WFH) guidelines for management of hemophilia screening tests for hemophilia
Interpretation of screening tests
| Possible diagnosis | PT (prothrombin time) | APTT* (activated partial thromboplastin time) | BT (bleeding time) | Platelet Count |
| Normal | Normal | Normal | Normal | Normal |
| VWD | Normal | Normal or prolonged* | Normal or prolonged | Normal or reduced |
*Results of APTT measurements are highly dependent on the laboratory method used for analysis
**The same pattern can occur in presence of FXI, FXII, prekallikrein, or high molecular weight kininogen deficiencies
Table 2: The 2nd edition World Federation of Hemophilia (WFH) guidelines for management of hemophilia severity classification criteria for hemophilia
Relationship of bleeding severity to clotting factor level
| Severity | Clotting Factor Level | Bleeding Episodes |
| Severe | <1 IU/dl (<0.01 IU/ml) or <1% of normal | Spontaneous bleeding into joints or muscles, predominantly in the absence of identifiable hemostatic challenge |
| Moderate | 1-5 IU/dl (0.01-0.05 IU/ml) or 1-5% of normal | Occasional spontaneous bleeding; prolongs bleeding with minor trauma or surgery |
| Mild | 5-40 IU/dl (0.05-0.40 IU/ml) or 5-<40% of normal | Severe bleeding with major trauma or surgery. Spontaneous bleeding is rare. |
Table 3: Laboratory Tests for Von Willebrand Disease Diagnosis and Classification, adapted from the National Heart, Lung, and Blood Institute
Initial Tests
| Diagnosis | VWF:RCO (IU per dL)* | VWF:AG (IU per dL)* † | Factor VIII |
| Type 1 | < 30 | < 30 | ↓ or normal |
| Type 2A | < 30 | < 30 to 200 | ↓ or normal |
| Type 2B | < 30 | < 30 to 200 | ↓ or normal |
| Type 2M | < 30 | < 30 to 200 | ↓ or normal |
| Type 2N | 30 to 200 | 30 to 200 | ↓ ↓ |
| Type 3 | < 3 | < 3 | ↓ ↓ ↓ (<10 IU per dL) |
| Low VWF | 30 to 50§ | 30 to 50§ | Normal |
| Normal | 50 to 200 | 50 to 200 | Normal |
Note: These values represent prototypical cases without additional VWF (or other disease) abnormalities. Exceptions occur, and repeat testing and clinical experience may be necessary for interpretation of laboratory test results. Arrows refer to an increase or decrease in the test result compared with the laboratory reference range.
[VWD = von Willebrand disease; VWF = von Willebrand factor; VWF:Ag = VWF antigen; VWF:RCo = VWF ristocetin cofactor activity]
*VWF levels of less than 30 IU per dL are recommended for the definite diagnosis of VWD (especially type 1 disease) because many persons in the United States have type O blood, which is associated with low VWF levels without VWD; bleeding symptoms are common in persons without VWD; and no abnormality in the VWF gene has been identified in many persons with mildly to moderately decreased VWF levels.
†VWF:Ag is less than 50 IU per dL in most patients with type 2A, 2B, or 2M VWD.
§— Does not preclude the diagnosis of VWD in patients with a VWF:RCo of 30 to 50 IU per dL if there is supporting clinical evidence or family history of VWD, and does not preclude the use of agents to increase VWF levels in those who have a VWF:RCo of 30 to 50 IU per dL and may be at risk of bleeding.
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
II. Vonvendi is considered medically necessary for any of the following FDA-approved conditions:
1. von Willebrand disease (VWD)
· Diagnosis of von Willebrand disease has been confirmed by blood coagulation and von Willebrand factor testing; AND
· Member is 18 years of age or older; AND
· Used as treatment of spontaneous and trauma-induced bleeding episodes in at least one of the following:
· Patients with mild, moderate, or severe VWD; OR
· Patients with mild or moderate VWD in whom the use of desmopressin acetate (DDAVP) is ineffective or contraindicated; AND
· Is NOT being used for routine prophylactic treatment of spontaneous bleeding episodes; AND
· Is NOT being used for Hemophilia A
· Used for perioperative management of bleeding
· 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).
III. When medically necessary, Vonvendi will be approved based on the following FDA approved dosing (see tables below).
1) Initial authorization periods vary by specific indication:
a) Control of acute bleeding episodes (hemorrhage)
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
o Unless otherwise specified, the authorization is valid for 1 month
2) 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.
Vonvendi
| Indication | Dose |
| Perioperative management of bleeding vWD | Elective surgical procedures
A dose of Vonvendi may be administered 12 to 24 hours prior to surgery to allow the endogenous factor VIII levels to increase to at least 30 IU/dL (minor surgery) or 60 IU/dL (major surgery).
Assess FVIII:C levels within 3 hours prior to surgery; if the FVIII:C levels are at or above the recommended minimum target levels, administer a dose of Vonvendi alone within 1 hour prior to the procedure. If the FVIII:C levels are below the recommended minimum target levels, administer recombinant factor VIII in addition to Vonvendi to raise VWF:RCo and FVIII:C.
For emergency surgery
Assess baseline VWF:RCo and FVIII:C levels within 3 hours prior to surgery. If not available, use weight based dosing calculation
Administer Vonvendi one hour before surgery with or without recombinant factor VIII and adjust the dose to raise VWF:RCo and FVIII:C to adequate level.
Continue to monitor the VWF:RCo and FVIII:C plasma levels after surgical procedure. |
| Control of bleeding episodes VWD | For each bleeding episode, administer the first dose of VONVENDI with an approved recombinant (non-von Willebrand factor containing) factor VIII if factor VIII baseline levels are below 40% or are unknown.
If recombinant factor VIII is required, give recombinant factor VIII within 10 minutes of completing VONVENDI infusion at a ratio of 1.3:1 (i.e., 30% more VONVENDI than recombinant factor VIII, based on the approximate mean recoveries of 1.5 and 2 IU/dL for VONVENDI and recombinant factor VIII, respectively).
Minor:
Loading dose: 40-50 IU/kg; Maintenance dose: 40-50 IU/kg every 8-24 hours as clinically required
Major:
Loading dose: 50-80 IU/kg; Maintenance dose: 40-60 IU/kg every 8-24 hours for approximately 2 to 3 days (as clinically required) |
IV. For continuing therapy, Vonvendi is considered medically necessary and approved when ALL of the following criteria are met:
· 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);
· Thromboembolic events (thromboembolism, pulmonary embolism);
o 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 Vonvendi to avoid sustained excessive VWF and FVIII activity levels.
· Development of neutralizing antibodies (inhibitors); AND
o Neutralizing antibodies 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 high levels of inhibitors to VWF or factor VIII, Vonvendi therapy may not be effective and infusion may lead to severe hypersensitivity reactions.
· Any increases in dose must be supported by an acceptable clinical rationale (i.e. weight gain, increase in breakthrough bleeding when patient is fully adherent to therapy, etc.).
· 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
· 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.
V. All other uses of Vonvendi are considered investigational.
Medicare Coverage:
Hemophilia Products – von Willebrand Factor (von Willebrand Disease): Wilate and Vonvendi ) are covered when NCD 110.3 and LCD L35111 criteria is met. For additional information and eligibility, refer to NCD 110.3 and L35111.
National Coverage Determination (NCD) for Anti-Inhibitor Coagulant Complex (AICC) (110.3). Available to be accessed at CMS National Coverage Determinations (NCDs) Alphabetical Index search page: https://www.cms.gov/medicare-coverage-database/indexes/ncd-alphabetical-index.aspx.
Local Coverage Determination (LCD): Hemophilia Factor Products (L35111). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/LcdSearch?_afrLoop=90769712476969#!%40%40%3F_afrLoop%3D90769712476969%26centerWidth%3D100%2525%26leftWidth%3D0%2525%26rightWidth%3D0%2525%26showFooter%3Dfalse%26showHeader%3Dfalse%26_adf.ctrl-state%3D63y7eftob_46.
Medicaid Coverage:
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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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.
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Index:
Hemophilia Products – von Willebrand Factor (von Willebrand Disease): Vonvendi
Vonvendi
von Willebrand Factor
von Willebrand Disease
References:
1. Wilate [package insert]. Hoboken, NJ; Octapharma USA; September 2019.
2. Vonvendi [package insert]. Westlake Village, CA; Baxalta US Inc.; February 2019.
3. 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.
4. 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.
5. 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.
6. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Access June 2016.
7. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
8. Mingot-Castellano, et al. Application of Pharmacokinetics Programs in Optimization of Haemostatic Treatment in Severe Hemophilia a Patients: Changes in Consumption, Clinical Outcomes and Quality of Life. Blood. 2014 December; 124 (21).
9. Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2014; 12:1935.
10. Guidelines for the management of hemophilia, 2nd edition. 2012 World Federation of Hemophilia. July 2012. Available at: https://www1.wfh.org/publication/files/pdf-1472.pdf. Accessed March 2018.
11. Collins PW, Chalmers E, Hart DP, et al. UK Haemophilia Centre Doctors. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). UK Haemophilia Centre Doctors Organization. Br J Haematol. 2013 Jan; 160(2): 153-70. Available on PubMed.
12. National Heart, Lung, and Blood Institute. The diagnosis, evaluation, and management of von Willebrand disease. Bethesda, Md.: National Institutes of Health; December 2007:36. NIH publication no. 08-5832. http://www.nhlbi.nih.gov/guidelines/vwd. Accessed March 7, 2018.
13. World Federation of Hemophilia. What is von Willebrand Disease (VWD)? Montreal, Quebec. Updated May 2014. https://www.wfh.org/en/page.aspx?pid=673. Accessed March 7, 2018.
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*
HCPCS
J7179
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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