ph-0059
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SCIG (immune globulin SQ): Hizentra®, Gammagard Liquid®, Gamunex®-C, Gammaked®, Hyqvia®, Cuvitru®, Cutaquig®, Xembify® Xembify®

Policy Number: PH-0059

Subcutaneous

 

Last Review Date: 10/01/2020

Date of Origin: 7/20/2010

Dates Reviewed: 09/2010, 12/2010, 03/2011, 06/2011, 09/2011, 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 09/2014, 12/2014, 03/2015, 06/2015, 09/2015, 12/2015, 03/2016, 06/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 04/2018, 06/2018, 10/2018, 01/2019, 08/2019, 10/2019, 10/2020

FOR PEEHIP Members Only – Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

  1. Length of Authorization

Initial coverage will be provided for 6 months and may be renewed annually thereafter.

  1. Dosing Limits

A.  Quantity Limit (max daily dose) [NDC Unit]:

Drug Name

Dose/ week

Dose/28 days

Hizentra

46 g

184 g

Gamunex-C & Gammaked

24 g

96 g

Gammagard liquid

24 g

96 g

HyQvia

17.5 g

69 g

Cuvitru

23 g

92 g

Cutaquig

24 g

96 g

Xembify

24 g

96 g

B.  Max Units (per dose and over time) [HCPCS Unit]:

Drug Name

Billable units/28 days

Hizentra

960 (PID)

1840 (CIDP)

Gamunex-C & Gammaked

192

Gammagard liquid

192

HyQvia

690

Cuvitru

920

Cutaquig

N/A (96 gms/28 days)

Xembify

960

  1. Initial Approval Criteria 1-8, 15,18

Coverage is provided in the following conditions:

  • Baseline values for BUN and serum creatinine obtained within 30 days of request; AND

Primary immunodeficiency (PID)/Wiskott -Aldrich syndrome

Such as: x-linked agammaglobulinemia, common variable immunodeficiency, transient hypogammaglobulinemia of infancy, IgG subclass deficiency with or without IgA deficiency, antibody deficiency with near normal immunoglobulin levels) and combined deficiencies (severe combined immunodeficiencies, ataxia-telangiectasia, x-linked lymphoproliferative syndrome) [list not all inclusive]

  • Patient is ≥ 2 years old [HyQvia and Cutaquig ONLY: patient must be ≥ 18 years old]; AND
  • Patient’s IgG level is <200 mg/dL OR both of the following
    • Patient has a history of multiple hard to treat infections as indicated by at least one of the following:
    • Four or more ear infections within 1 year
    • Two or more serious sinus infections within 1 year
    • Two or more months of antibiotics with little effect
    • Two or more pneumonias within 1 year
    • Recurrent or deep skin abscesses
    • Need for intravenous antibiotics to clear infections
    • Two or more deep-seated infections including septicemia; AND
    • The patient has a deficiency in producing antibodies in response to vaccination; AND
    • Titers were drawn before challenging with vaccination; AND
    • Titers were drawn between 4 and 8 weeks of vaccination

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) [Hizentra ONLY] Ф

  • Patient must be ≥ 18 years old; AND
  • Physician has assessed baseline disease severity utilizing an objective measure/tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.); AND
    • Used as initial maintenance therapy for prevention of disease relapses after treatment and stabilization with intravenous immunoglobulin (IVIG)§; OR
    • Used for re-initiation of maintenance therapy after experiencing a relapse and requiring re-induction therapy with IVIG (see Section IV for criteria)

§ Refer to the Immune Globulins medical necessity criteria (Document Number: IC-0071) for the relevant intravenous criteria requirements

FDA Approved Indication(s); Compendia Recommended Indication(s); Ф Orphan Drug

  1. Renewal Criteria 1-8, 15,18

Coverage can be renewed for 1 year based upon the following criteria:

  • Patient continues to meet the universal and other indication-specific relevant criteria identified in section III ; AND
  • Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity/anaphylaxis, thrombosis, aseptic meningitis syndrome, hemolytic anemia, hyperproteinemia, acute lung injury, etc.; AND
  • BUN and serum creatinine obtained within the last 6 months and the concentration and rate of infusion have been adjusted accordingly; AND

Primary immunodeficiency (PID)/Wiskott -Aldrich syndrome

  • Disease response as evidenced by one or more of the following:
    • Decrease in the frequency of infection
    • Decrease in the severity of infection

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) [Hizentra ONLY]

  • Renewals will be authorized for patients that have demonstrated a beneficial clinical response to maintenance therapy, without relapses, based on an objective clinical measuring tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.); OR
  • Patient is re-initiating maintenance therapy after experiencing a relapse while on Hizentra; AND
    • Patient improved and stabilized on IVIG treatment: AND
    • Patient was NOT receiving maximum dosing of Hizentra prior to relapse
  1. Dosage/Administration

Dosing should be calculated using adjusted body weight if one or more of the following criteria are met:

  • Patient’s body mass index (BMI) is 30 kg/m2 or more; OR
  • Patient’s actual body weight is 20% higher than his or her ideal body weight (IBW)

Use the following dosing formulas to calculate the adjusted body weight (round dose to nearest 5 gram increment in adult patients)

Dosing formulas

BMI = 703 x (weight in pounds/height in inches2)

IBW(kg) for males = 50 + [2.3 (height in inches – 60)]

IBW(kg) for females = 45.5 + [2.3 x (height in inches – 60)]

Adjusted body weight = IBW + 0.5 (actual body weight – IBW)

This information is not meant to replace clinical decision making when initiating or modifying medication therapy and should only be used as a guide. Patient-specific variables should be taken into account.

Indication

Dose

Chronic Inflammatory Demyelinating Polyneuropathy

Hizentra ONLY:

  • Initiate therapy 1 week after the last IVIG dose
  • The recommended subcutaneous dose is 0.2 g/kg (1 mL/kg) body weight per week, administered in 1 or 2 sessions over 1 or 2 consecutive days.
  • If CIDP symptoms worsen, consider re-initiating treatment with an IVIG while discontinuing Hizentra.
  • If improvement and stabilization are observed during IVIG treatment, consider reinitiating Hizentra at the dose of 0.4 g/kg body weight per week, administered in 2 sessions per week over 1 or 2 consecutive days, while discontinuing IVIG.
  • If CIDP symptoms worsen on the 0.4 g/kg body weight per week dose, consider re-initiating therapy with an IVIG while discontinuing Hizentra.

Primary immune deficiency including Wiskott-Aldrich Syndrome

Hizentra:

  • Weekly dose: 1.37*(previous IVIG dose(g)/number of weeks between IVIG doses)
  • Biweekly dose: twice the weekly dose (using calculation above)

Gamunex-C/Gammaked/Gammagard Liquid:

  • Weekly dose: 1.37*(previous IVIG dose(g)/number of weeks between IVIG doses)

HyQvia:

  • Naïve to IgG or switching from SCIG: 300 to 600 mg/kg at 3 to 4 week intervals after initial ramp-up*
  • Switching from IGIV: use the same dose and frequency as the previous IV treatment after initial ramp-up*

Xembify:

  • Switching from IVIG :
    • Start treatment one week after the last IVIG infusion.
    • Weekly dose: 1.37*(previous monthly (or every 3- week) IVIG dose in grams)/number of weeks between IVIG doses)
  • To convert the dose in grams to mL, multiply the calculated initial SQ dose (in grams) by 5
  • Provided the total weekly dose is maintained, any dosing interval from daily up to weekly will achieve similar systemic IgG exposure when administered regularly at steady-state.
  • Switching from SCIG
    • Weekly dose (in grams) should be same as the weekly dose of prior SCIG treatment (in grams)

Cuvitru:

  • Switching from IVIG or HyQvia:
    • Weekly dose: 1.30*(previous IVIG or HyQvia dose (g)/number of weeks between IVIG or HyQvia doses)
    • May be administered from daily up to every two weeks (biweekly)
    • Biweekly dose: twice the weekly dose (using calculation above)
    • Frequent dosing (2-7 times per week): divide the calculated weekly dose by the desired number of times per week
  • Switching from SCIG
    • Weekly dose (in grams) should be same as the weekly dose of prior SCIG treatment (in grams)
    • Biweekly dose: multiply the calculated weekly dose by 2
    • Frequent dosing (2-7 times per week): divide the calculated weekly dose by the desired number of times per week

Cutaquig:

(Start treatment one week after the last IVIG or SCIG infusion. Ensure that patients have received IVIG or SCIG treatment at regular intervals for at least 3 months)

  • Switching from IVIG to Cutaquig
  • Establish the initial weekly dose by converting the monthly IVIG dose into an equivalent weekly dose and increasing it using a dose adjustment factor
  • To calculate the initial weekly dose, divide the monthly IVIG dose in grams by the number of weeks between IGIV infusions and then multiply this value with a Dose Adjustment Factor of 1.40

Initial weekly dose = Previous IGIV dose (in grams) x 1.40/Number of weeks between IGIV doses

  • To convert the dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 6
  • Provided the total weekly dose is maintained, any dosing interval from daily up to weekly can be used and will result in systemic IgG exposure that is comparable to the previous IGIV treatment
  • Switching from SCIG to Cutaquig
  • It is recommended to maintain the same weekly dosing (in grams) of Cutaquig that was used for the previous SCIG therapy (in grams)
  • To convert the dose (in grams) to milliliters (mL), multiply the calculated dose (in grams) by 6
  • Obtain a trough IgG level before switching, monitor clinical response and check the trough IgG level 2 to 3 months after initiating Cutaquig

Dosing for immunoglobulin products is highly variable depending on numerous patient specific factors, indication(s), and the specific product selected. For specific dosing regimens refer to current prescribing literature.

*HyQvia initial treatment interval/dosage ramp-up schedule

Week

Infusion Number

3-week treatment interval

4-week treatment interval

1

1st infusion

Dose in Grams X 0.33

Dose in Grams X 0.25

2

2nd infusion

Dose in Grams X 0.67

Dose in Grams X 0.50

4

3rd infusion

Total Dose in Grams

Dose in Grams X 0.75

7

4th infusion

N/A

Total Dose in Grams

  1. Billing Code/Availability Information

HCPCS code & NDC:

Drug Name*

Manufacturer

HCPCS Code

1 Billable unit

NDC

IgG (grams) per SDV

Volume (mL)

Hizentra 20%

CSL Behring AG

J1559 – Injection, immune globulin (Hizentra), 100 mg

100 mg

44206-0451-01

1

5

44206-0452-02

2

10

44206-0454-04

4

20

44206-0455-10

10

50

Gammaked 10%

Kedrion Biopharma, Inc.

J1561 Injection, immune globulin, (Gamunex-C/ Gammaked), non-lyophilized (e.g. liquid), 500 mg

500 mg

76125-0900-01

1

10

76125-0900-25

2.5

25

76125-0900-50

5

50

76125-0900-10

10

100

76125-0900-20

20

200

Gamunex-C 10%

Grifols Therapeutics

J1561 –  Injection, immune globulin, (Gamunex-C/Gammaked), non-lyophilized (e.g. liquid), 500 mg

500 mg

13533-0800-12

1

10

13533-0800-15

2.5

25

13533-0800-20

5

50

13533-0800-71

10

100

13533-0800-24

20

200

13533-0800-40

40

400

Gammagard Liquid 10%

Baxter Healthcare Corporation

J1569 – Injection, immune globulin, (Gammagard liquid), non-lyophilized, (e.g. liquid), 500 mg

500 mg

00944-2700-02

1

10

00944-2700-03

2.5

25

00944-2700-04

5

50

00944-2700-05

10

100

00944-2700-06

20

200

00944-2700-07

30

300

HyQvia 10% (with Recombinant Human Hyaluronidase 160 U/mL)

Baxter Healthcare Corporation

J1575 – Injection, immune globulin/ hyaluronidase, (Hyqvia), 100 mg immune globulin

100 mg

00944-2510-02

2.5

25

00944-2511-02

5

50

00944-2512-02

10

100

00944-2513-02

20

200

00944-2514-02

30

300

Cuvitru 20%

Baxalta US Inc.

J1555Injection, immune globulin (Cuvitru), 100 mg

100 mg

00944-2850-01

1

5

00944-2850-03

2

10

00944-2850-05

4

20

00944-2850-07

8

40

Cutaquig 16.5%

Octapharma

J3590 – unclassified biologic; C9399 – unclassified drug or biological

N/A

68892-0810-01

1

6

68892-0810-02

1.65

10

68892-0810-03

2

12

68892-0810-04

3.3

20

68892-0810-05

4

24

68892-0810-06

8

48

Xembify 20%

Grifols

J1558 – Injection, immune globulin (Xembify), 100 mg

100 mg

13533-0810-05

1

5

13533-0810-10

2

10

13533-0810-20

4

20

13533-0810-50

10

50

Immune Globulin, Human, Subcutaneous

N/A

J3590 – unclassified biologic; C9399 – unclassified drug or biological

N/A

N/A

N/A

N/A

*90284 – immune globulin (SCIg), human, for use in subcutaneous infusions

  1. References
  1. Xembify [package insert]. Triangle Park, NC; Grifols; July 2019. Accessed August 2020.
  2. Cutaquig [package insert]. Stokholm, Sweden; Octapharma; November 2020. Accessed August 2020.
  3. Hizentra [package insert]. Bern, Switzerland; CSL Behring AG; March 2020. Accessed August 2020.
  4. HyQvia [package insert]. Westlake Village, CA; Baxter Healthcare Corporation; February 2020. Accessed August 2020.
  5. Cuvitru [package insert]. Westlake Village, CA; Baxalta US Inc.; May 2019. Accessed August 2020.
  6. Gammagard Liquid [package insert]. Westlake Village, CA; Baxter Healthcare Corporation; June 2016. Accessed August 2020.
  7. Gamunex®-C [package insert]. Research Triangle, NC; Grifols Therapeutics, Inc.; January 2020. Accessed August 2020.
  8. Gammaked™ [package insert]. Research Triangle, NC; Grifols Therapeutics, Inc.; June 2018. Accessed August 2020.
  9. Jeffrey Modell Foundation Medical Advisory Board, 2013.  10 Warning Signs of Primary Immunodeficiency.  Jeffrey Modell Foundation, New York, NY
  10. Orange J, Hossny E, Weiler C, et al. Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2006;117(4 Suppl): S525-53.
  11. Orange JS, Ballow M, Stiehm, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: A working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol Vol 130 (3).
  12. Bonilla FA, Khan DA, Ballas ZK, et al. Practice Parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015 Nov;136(5):1186-205.e1-78.
  13. Emerson GG, Herndon CN, Sreih AG. Thrombotic complications after intravenous immunoglobulin therapy in two patients. Pharmacotherapy. 2002;22:1638-1641.
  14. Department of Health (London). Clinical Guidelines for Immunoglobulin Use: Update to Second Edition. August, 2011.
  15. Provan, Drew, et al. "Clinical guidelines for immunoglobulin use." Department of Health Publication, London (2008).
  16. Dantal J. Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk. Am J Nephrol 2013;38:275-284.
  17. Immune Deficiency Foundation. Diagnostic & Clinical Care Guidelines for Primary Immunodeficiency Diseases. 3rd Ed. 2015. Avail at: https://primaryimmune.org/sites/default/files/publications/2015-Diagnostic-and-Clinical-Care-Guidelines-for-PI_1.pdf.
  18. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017 Mar;139(3S):S1-S46.
  19. Alonso W, Vandeberg P, Lang J, et al. Immune globulin subcutaneous, human 20% solution (Xembify®), a new high concentration immunoglobulin product for subcutaneous administration. Biologicals. 2020;64:34-40.
  20. Kobayashi RH, Gupta S, Melamed I, et al. Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (octanorm [cutaquig®]) in the Treatment of Patients with Primary Immunodeficiencies. Front Immunol. February 2019 | Volume 10 | Article 40.
  21. van Schaik IN, Bril V, van Geloven N, et al. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP), a multicenter randomised double-blind placebo-controlled trial: the PATH Study. Lancet Neurol. 2017;17(1):35-46.
  22. Hagan JB, Fasano MB, Spector S, et al. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010;30(5):734-745.
  23. Jolles S, Borte M, Nelson R, et al. Long-term efficacy, safety, and tolerability of Hizentra for treatment of primary immunodeficiency disease. Clin Immunol. 2014;150(2):161-169.
  24. Wasserman RL, Melamed I, Nelson RP Jr, et al. Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011;50(6):405-414.
  25. Wasserman RL, Melamed I, Kobrynski L, et al. Efficacy, Safety, and Pharmacokinetics of a 10% Liquid Immune Globulin Preparation (GAMMAGARD LIQUID, 10%) Administered Subcutaneously in Subjects with Primary Immunodeficiency Disease. J Clin Immunol. 2011 Mar 22. [Epub ahead of print]
  26. Food and Drug Administration. Safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-efficacy-and-pharmacokinetic-studies-support-marketing-immune-globulin-intravenous-human. Accessed May 28, 2019
  27. Wasserman RL, Melamed I, Stein MR, et al; and IGSC, 10% with rHuPH20 Study Group. Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol. 2012;130(4):951-957.
  28. Suez D, Stein M, Gupta S, et al. Efficacy, safety, and pharmacokinetics of a novel human immune globulin subcutaneous, 20% in patients with primary immunodeficiency diseases in North America. J Clin Immunol. 2016;36(7):700-712.
  29. Roifman CM, Schroeder H, Berger M, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency: a randomized double-blind trial. Int Immunopharmacol. 2003;3(9):1325-1333.
  30. Roifman CM, Schroeder H, Berger M, et al, and the IGIV-C in PID Study Group. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency: a randomized double-blind trial. Int Immunopharmacol. 2003;3:1325-1333.

Appendix 1 – Covered Diagnosis Codes (All Products)

ICD-10

ICD-10 Description

D80.0

Hereditary hypogammaglobulinemia

D80.1

Nonfamilial hypogammaglobulinemia

D80.2

Selective deficiency of immunoglobulin A [IgA]

D80.3

Selective deficiency of immunoglobulin G [IgG] subclasses

D80.4

Selective deficiency of immunoglobulin M [IgM]

D80.5

Immunodeficiency with increased immunoglobulin M [IgM]

D80.7

Transient hypogammaglobulinemia of infancy

D81.0

Severe combined immunodeficiency [SCID] with reticular dysgenesis

D81.1

Severe combined immunodeficiency [SCID] with low T- and B-cell numbers

D81.2

Severe combined immunodeficiency [SCID] with low or normal B-cell numbers

D81.6

Major histocompatibility complex class I deficiency

D81.7

Major histocompatibility complex class II deficiency

D81.89

Other combined immunodeficiencies

D81.9

Combined immunodeficiency, unspecified

D82.0

Wiskott-Aldrich syndrome

D83.0

Common variable immunodeficiency with predominant abnormalities of B-cell numbers and function

D83.2

Common variable immunodeficiency with autoantibodies to B- or T-cells

D83.8

Other common variable immunodeficiencies

D83.9

Common variable immunodeficiency, unspecified

Additional covered diagnosis codes applicable to Hizentra ONLY:

ICD-10

ICD-10 Description

G61.81

Chronic inflammatory demyelinating polyneuritis

G61.89

Other inflammatory polyneuropathies

G62.89

Other specified polyneuropathies

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):  N/A

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC