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Ultomiris® (ravulizumab-cwvz)

Policy Number: PH-0427

Intravenous/Subcutaneous

 

Last Review Date: 09/05/2023

Date of Origin: 02/04/2019

Dates Reviewed: 02/2019, 10/2019, 12/2019, 11/2020, 07/2021, 10/2021, 06/2022, 09/2022, 9/2023

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

Coverage will be provided for twelve (12) months and may be renewed.

  1. Dosing Limits

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

  • Ultomiris 10 mg/mL** – 30 mL SDV: 10 vials on day zero followed by 13 vials starting on day 14 and every 8 weeks thereafter
  • Ultomiris 100 mg/mL – 3 mL SDV: 10 vials on day zero followed by 13 vials starting on day 14 and every 8 weeks thereafter
  • Ultomiris 100 mg/mL – 11 mL SDV: 3 vials on day zero followed by 3 vials starting on day 14 and every 8 weeks thereafter
  • Ultomiris 245 mg/3.5 mL single-dose cartridge on-body delivery system: 2 on-body delivery systems weekly

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

  • Ultomiris IV
    • PNH/aHUS/gMG: 300 units on Day 0 followed by 360 units on Day 14 and every 8 weeks thereafter
  • Ultomiris SQ
    • PNH/aHUS: 49 units weekly
  1. Initial Approval Criteria 1

Depending on member benefits, additional criteria may apply for coverage of this drug in an outpatient facility setting. Verify any Site of Service requirements with the member’s plan and refer to the Voluntary Site of Service Policy or the Mandatory Site of Service Policy for additional information.

Coverage is provided in the following conditions:

  • Patient is at least 1 month of age (unless otherwise specified); AND
  • Prescriber is enrolled in the Ultomiris Risk Evaluation and Mitigation Strategy (REMS) program; AND

Universal Criteria 1

Submission of medical records related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation via direct upload through the PA web portal or by fax.

  • Patients must be administered a meningococcal vaccine at least two weeks prior to initiation of therapy and will continue to be revaccinated according to current medical guidelines for vaccine use (If urgent Ultomiris therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with two weeks of antibacterial drug prophylaxis.); AND
  • Will not be used in combination with other immunomodulatory biologic therapies (e.g., efgartigimod, eculizumab, pegcetacoplan, satralizumab, inebilizumab, rozanolixizumab, etc.); AND

Paroxysmal Nocturnal Hemoglobinuria (PNH) † Ф 1,4,8,9,18

  • Used as switch therapy; AND
    • Patient is currently receiving treatment with eculizumab and has shown a beneficial disease response and absence of unacceptable toxicity while on therapy; OR
  • Patient is complement inhibitor treatment-naïve; AND
    • Diagnosis must be confirmed by detection of PNH clones of at least 5% by flow cytometry testing; AND
      • Patient has at least 2 different glycosylphosphatidylinositol (GPI) protein deficiencies (e.g., CD55, CD59, etc.) within at least 2 different cell lines (e.g., granulocytes, monocytes, erythrocytes); AND
      • Patient has laboratory evidence of significant intravascular hemolysis (i.e., LDH ≥1.5 x ULN) with symptomatic disease and at least one other indication for therapy from the following (regardless of transfusion dependence):
  • Patient has symptomatic anemia (i.e., hemoglobin < 7 g/dL or hemoglobin < 10 g/dL, in at least two independent measurements in a patient with cardiac symptoms)
  • Presence of a thrombotic event related to PNH
  • Presence of organ damage secondary to chronic hemolysis (i.e., renal insufficiency, pulmonary insufficiency/hypertension)
  • Patient is pregnant and potential benefit outweighs potential fetal risk
  • Patient has disabling fatigue
  • Patient has abdominal pain (requiring admission or opioid analgesia), dysphagia, or erectile dysfunction; AND
      • Documented baseline values for one or more of the following (necessary for renewal): serum lactate dehydrogenase (LDH), hemoglobin level, packed RBC transfusion requirement, and history of thrombotic events 

Atypical Hemolytic Uremic Syndrome (aHUS) † 1,5,7,19-21

  • Used as switch therapy; AND
    • Patient is currently receiving treatment with eculizumab and has shown a beneficial disease response and absence of unacceptable toxicity while on therapy; OR
  • Patient is complement inhibitor treatment-naïve; AND
    • Patient shows signs of thrombotic microangiopathy (TMA) (e.g., changes in mental status, seizures, angina, dyspnea, thrombosis, increasing blood pressure, decreased platelet count, increased serum creatinine, increased LDH, etc.); AND
    • Thrombotic Thrombocytopenic Purpura (TTP) has been ruled out by evaluating ADAMTS-13 level (ADAMTS-13 activity level ≥ 10%); AND
    • Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS) has been ruled out; AND
    • Other causes have been ruled out such as coexisting diseases or conditions (e.g., bone marrow transplantation, solid organ transplantation, malignancy, autoimmune disorder, drug-induced, malignant hypertension, HIV infection, Streptococcus pneumoniae sepsis or known genetic defect in cobalamin C metabolism, etc.); AND
    • Documented baseline values for one or more of the following (necessary for renewal): serum lactate dehydrogenase (LDH), serum creatinine/eGFR, platelet count, and dialysis requirement

Generalized Myasthenia Gravis (gMG) Ф 1,11,12-17

For PEEHIP Member Only:

  • Patients must have tried and failed, had an inadequate response or intolerance to, or contraindication to Vyvgart or Vyvgart Hytrulo prior to consideration of Ultomiris for Myasthenia Gravis.
  • Used as switch therapy; AND
    • Patient is at least 18 years of age; AND
    • Patient is currently receiving treatment with eculizumab and has shown a beneficial disease response and absence of unacceptable toxicity while on therapy; OR
  • Patient is complement inhibitor treatment-naïve; AND
  • Patient is at least 18 years of age; AND
  • Patient has Myasthenia Gravis Foundation of America (MGFA) Clinical Classification of Class II to IV disease§; AND
  • Patient has a positive serologic test for anti-acetylcholine receptor (AChR) antibodies; AND
  • Patient has had a thymectomy (Note: Applicable only to patients with thymomas OR non-thymomatous patients who are 50 years of age or younger); AND
  • Physician has assessed objective signs of neurological weakness and fatiguability on a baseline neurological examination (e.g., including, but not limited to, the Quantitative Myasthenia Gravis [QMG] score, etc.); AND
  • Patient has a baseline MG-Activities of Daily Living (MG-ADL) total score of ≥6; AND
      • Patient has had an inadequate response after a minimum one-year trial of concurrent use with two (2) or more immunosuppressive therapies (e.g., corticosteroids plus an immunosuppressant such as azathioprine, cyclosporine, mycophenolate, etc.); OR
      • Patient required chronic treatment with plasmapheresis or plasma exchange (PE) or intravenous immunoglobulin (IVIG) in addition to immunosuppressant therapy; AND
  • Patient will avoid or use with caution medications known to worsen or exacerbate symptoms of MG (e.g., certain antibiotics, beta-blockers, botulinum toxins, hydroxychloroquine, etc.)

§Myasthenia Gravis Foundation of America (MGFA) Disease Clinical Classification 14:

  • Class I: Any ocular muscle weakness; may have weakness of eye closure. All other muscle strength is normal.
  • Class II: Mild weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.
    • IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
    • IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.
  • Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.
    • IIIa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
    • IIIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.
  • Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.
    • IVa. Predominantly affecting limb, axial muscles, or both. May also have lesser involvement of oropharyngeal muscles.
    • IVb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have lesser or equal involvement of limb, axial muscles, or both.
  • Class V: Defined as intubation, with or without mechanical ventilation, except when employed during routine postoperative management. The use of a feeding tube without intubation places the patient in class IVb.

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

  1. Renewal Criteria 1

Coverage may be renewed 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: serious meningococcal infections (septicemia and/or meningitis), infusion-related reactions, other serious infections, etc.; AND

Paroxysmal Nocturnal Hemoglobinuria (PNH) 1,4,8,18

  • Patient has not developed severe bone marrow failure syndrome (i.e., aplastic anemia or myelodysplastic syndrome) OR experienced a spontaneous disease remission OR received curative allogeneic stem cell transplant; AND
  • Disease response indicated by one or more of the following:
    • Decrease in serum LDH from pretreatment baseline
    • Stabilization/improvement in hemoglobin level from pretreatment baseline
    • Decrease in packed RBC transfusion requirement from pretreatment baseline (i.e., reduction of at least 30%)
    • Reduction in thromboembolic events

Atypical Hemolytic Uremic Syndrome (aHUS) 1,5,7

  • Disease response indicated by one or more of the following:
  • Decrease in serum LDH from pretreatment baseline
  • Stabilization/improvement in serum creatinine/eGFR from pretreatment baseline
  • Increase in platelet count from pretreatment baseline
  • Decrease in plasma exchange/infusion requirement from pretreatment baseline

Generalized Myasthenia Gravis (gMG) 1,11-17

  • Patient has had an improvement (i.e., reduction) of at least 1-point from baseline in the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) total score Δ; AND
  • Improvement in muscle strength testing with fatigue maneuvers as evidenced on neurologic examination when compared to baseline

[Δ May substitute an improvement of at least 1-point from baseline in the Quantitative Myasthenia Gravis (QMG) total score, if available]

Switch Therapy From Eculizumab to Ravulizumab

  • Refer to Section III for criteria
  1. Dosage/Administration 1

Indication

Dose

Paroxysmal nocturnal hemoglobinuria (PNH);

Atypical Hemolytic Uremic Syndrome (aHUS);

Generalized Myasthenia Gravis (gMG)

IV Dosing for Complement-Inhibitor Therapy Naïve*

Administer the INTRAVENOUS doses based on the patient’s body weight. Starting 2 weeks after the loading dose, begin maintenance doses once every 4 weeks or every 8 weeks (depending on body weight)

Indications

Body Weight Range

Loading Dose (mg)

Maintenance Dose (mg)

Dosing Interval

PNH, aHUS

5 kg to <10 kg

600

300

Every 4 weeks

10 kg to <20 kg

600

600

20 kg to <30 kg

900

2,100

Every 8 weeks

30 kg to <40 kg

1,200

2,700

PNH, aHUS, gMG

40 kg to <60 kg

2,400

3,000

Every 8 weeks

60 kg to <100 kg

2,700

3,300

100 kg or greater

3,000

3,600

IV Dosing for Switch Therapy from Eculizumab OR Ravulizumab SQ to Ravulizumab IV*

Population

Weight-based Ravulizumab IV Loading Dose

Time of First Ravulizumab IV Weight-based Maintenance Dose

Currently treated with eculizumab

At time of next scheduled eculizumab dose

2 weeks after ravulizumab IV loading dose

Currently treated with ravulizumab SQ on-body delivery system§

Not applicable

1 week after last ravulizumab SQ maintenance dose

SQ Dosing for Complement-Inhibitor Therapy Naïve §

PNH & aHUS (adult patients weighing ≥40 kg ONLY): 490 mg SQ via on-body injector once weekly starting 2 weeks after the initial IV weight-based loading dose (see IV weight-based dosing table above)

SQ Dosing for Switch Therapy from Eculizumab OR Ravulizumab IV to Ravulizumab SQ §

Population

Weight-based Ravulizumab IV Loading Dose

Time of First Ravulizumab SQ Maintenance Dose

Currently treated with eculizumab

At time of next scheduled eculizumab dose

2 weeks after ravulizumab IV loading dose

Currently treated with ravulizumab IV

Not applicable

8 weeks after last ravulizumab IV maintenance dose

§ Adult patients with PNH and aHUS only

*Note: For Supplemental Dose Therapy after plasma exchange (PE), plasmapheresis (PP), and intravenous immunoglobulin (IVIg), please refer to the package insert for appropriate dosing.

  1. Billing Code/Availability Information

HCPCS Code:

  • J1303 − Injection, ravulizumab-cwvz, 10 mg; 1 billable unit = 10 mg

NDC(s):

  • Ultomiris 300 mg/3 mL single-dose vial for injection: 25682-0025-xx
  • Ultomiris 300 mg/30 mL single-dose vial for injection: 25682-0022-xx**
  • Ultomiris 1,100 mg/11 mL single-dose vial for injection: 25682-0028-xx
  • Ultomiris 245 mg/3.5 mL single-dose cartridge on-body subcutaneous delivery system: 25682-0031-xx

**Note: This NDC has been discontinued as of 06/11/2021.

  1. References
  1. Ultomiris [package insert]. Boston, MA; Alexion Pharmaceuticals, Inc; July 2022. Accessed August 2023.
  2. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Borowitz MJ, Craig FE, DiGiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, Wittwer CT, Richards SJ. Cytometry B Clin Cytom. 2010 Jul;78(4):211-30. doi: 10.1002/cyto.b.20525.
  3. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1. 106(12):3699-709.
  4. Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines.  Am J Blood Res. 2016;6(2): 19-27.
  5. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016 Jan;31(1):15-39.
  6. Taylor CM, Machin S, Wigmore SJ, et al. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010 Jan;148(1):37-47.
  7. Cheong HI, Kyung Jo S, Yoon SS, et al. Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea. J Korean Med Sci. 2016 Oct;31(10):1516-1528.
  8. Brodsky RA, Peffault de Latour R, Rottinghaus ST, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2020 Jan 16. pii: haematol.2019.236877. doi: 10.3324/haematol.2019.236877. [Epub ahead of print]
  9. Patriquin CJ, Kiss T, Caplan S, et al. How we treat paroxysmal nocturnal hemoglobinuria: A consensus statement of the Canadian PNH Network and review of the national registry. Eur J Haematol. 2019;102(1):36. Epub 2018 Oct 25.
  10. Lee H, Kang E, Kang HG, et al. Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome. Korean J Intern Med. 2020;35(1):25-40. doi:10.3904/kjim.2019.388.
  11. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis-Executive Summary. Neurology. 2016 Jul 26; 87(4): 419-25.
  12. Vu T, Meisel A, Mantegazza R, et al. Efficacy and Safety of Ravulizumab, a Long-acting Terminal Complement Inhibitor, in Adults with Anti-Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: Results from the Phase 3 CHAMPION MG Study (P1-1.Virtual). Neurology May 2022, 98 (18 Supplement) 791.
  13. Narayanaswami P, Sanders D, Wolfe G, Benatar M, et al. International consensus guidance for management of myasthenia gravis, 2020 update. Neurology® 2021;96:114-122. doi:10.1212/WNL.0000000000011124.
  14. Jayam-Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia gravis: a review. Autoimmune Dis. 2012;2012:874680. doi:10.1155/2012/874680
  15. Gronseth GS, Barohn R, Narayanaswami P. Practice advisory: Thymectomy for myasthenia gravis (practice parameter update): Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2020;94(16):705. Epub 2020 Mar 25.
  16. Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: Association of British Neurologists’ management guidelines. Pract Neurol 2015; 15: 199-206.
  17. Institute for Clinical and Economic Review. Eculizumab and Efgartigimod for the Treatment of Myasthenia Gravis: Effectiveness and Value. Draft evidence report. July 22, 2021. https://icer.org/wp-content/uploads/2021/03/ICER_Myasthenia-Gravis_Draft-Evidence-Report_072221.pdf. Accessed December 22, 2021.
  18. Cançado RD, Araújo AdS, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematology, Transfusion and Cell Therapy, v43, Iss3, 2021, 341-348.  ISSN 2531-1379, https://doi.org/10.1016/j.htct.2020.06.006.
  19. Kulagin A, Chonat S, Maschan A, et al. Pharmacokinetics, pharmacodynamics, efficacy, and safety of ravulizumab in children and adolescents with paroxysmal nocturnal hemoglobinuria: interim analysis of a phase 3, open-label study. Presented at the European Hematology Association 2021 Virtual Congress, June 9-17, 2021.
  20. Tanaka K, Adams B, Aris AM, et al. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021 Apr;36(4):889-898. doi: 10.1007/s00467-020-04774-2.
  21. Rondeau E, Scully M, Ariceta G, et al; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. doi: 10.1016/j.kint.2020.01.035.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

D59.32

Hereditary hemolytic-uremic syndrome

D59.39

Other hemolytic-uremic syndrome

D59.5

Paroxysmal nocturnal hemoglobinuria [Marchiafava-Micheli]

G70.00

Myasthenia gravis without (acute) exacerbation

G70.01

Myasthenia gravis with (acute) exacerbation

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 Articles (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: https://wyww.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

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

 

 

 

ULTOMIRIS® (ravulizumab-cwvz) Prior Auth Criteria
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