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Ravulizumab-cwvz (Ultomiris® )

Commercial Drug Policy
Version Date: December 2024

Restricted Product(s):

  • ravulizumab-cwvz (Ultomiris® ) intravenous infusion for administration by a healthcare professional

FDA Approved Use:

  • For treatment of adults and pediatric patients one month of age or older with paroxysmal nocturnal hemoglobinuria (PNH)
  • For treatment of adults and pediatric patients one month of age or older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA)
    • Limitation of use: Not for treatment of Shiga toxin E. coli related hemolytic uremic syndrome
  • For treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive
  • For treatment of adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody-positive

Criteria for Medical Necessity:

The restricted product(s) may be considered medically necessary when the following criteria are met: 

Initial Criteria for Approval: 

  1. The patient has a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) [medical record documentation required]; AND 
    1. The patient is 1 month of age or older; AND 
    2. The patient has not received prior treatment with a complement inhibitor (i.e., eculizumab [Soliris® ]) [medical record documentation required]; AND
      1. The diagnosis has been confirmed by flow cytometry showing reduced levels of GPI-anchored proteins in at least two peripheral blood cell lines and a clone size of at least 5% [medical record documentation required]; AND
      2. The patient has a lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal at screening [medical record documentation required]; AND 
      3. The patient has at least one PNH sign or symptom (e.g., fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin < 10 g/dL], history of a major adverse vascular event [including thrombosis], dysphagia, erectile dysfunction or history of red blood cell transfusion due to PNH) [medical record documentation required]; AND
      4. The patient has received a meningococcal vaccination at least two weeks prior to starting therapy with the requested agent [medical record documentation required]; AND
      5. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat PNH (e.g., eculizumab, iptacopan, pegcetacoplan) [medical record documentation required]; OR 
    3. The patient is currently receiving complement inhibitor therapy with eculizumab (Soliris® ) and switching to the requested product [medical record documentation required]; AND
      1. The diagnosis has been confirmed by flow cytometry at baseline prior to starting complement inhibitor therapy with eculizumab showing reduced levels of GPI-anchored proteins in at least two peripheral blood cell lines and a clone size of at least 5% [medical record documentation required]; AND 
      2. The patient has been receiving complement inhibitor therapy with eculizumab for at least 6 months and is clinically stable, with an LDH level ≤ 1.5 times the upper limit of normal [medical record documentation required]; AND
      3. The patient has received a meningococcal vaccination within 3 years of starting therapy with the requested agent [medical record documentation required]; AND 
      4. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat PNH (e.g., eculizumab, iptacopan, pegcetacoplan) [medical record documentation required]; OR
  2. The patient has a diagnosis of atypical hemolytic uremic syndrome (aHUS) [medical record documentation required]; AND
    1. The patient is 1 month of age or older; AND
    2. The patient has evidence of complement-mediated thrombotic microangiopathy (TMA) (e.g., low platelet count, hemolysis [breaking of red blood cells inside of blood vessels], decreased kidney function) [medical record documentation required]; AND
    3. The patient does NOT have Shiga toxin E.coli related hemolytic uremic syndrome (STEC-HUS) [medical record documentation required]; AND
    4. The patient has received a meningococcal vaccine at least two weeks but no more than three years prior to starting therapy with the requested agent [medical record documentation required]; AND 
    5. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat aHUS (e.g., eculizumab) [medical record documentation required]; OR
  3. The patient has a diagnosis of generalized myasthenia gravis (gMG) [medical record documentation required]; AND
    1. The patient is 18 years of age or older; AND 
    2. ALL of the following:
      1. The patient has a positive serological test for anti-AChR antibodies [medical record documentation required]; AND
      2. The patient has a Myasthenia Gravis Foundation of America (MGFA) clinical classification class of II to IV; AND 
      3. The patient has a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 6 or higher; AND
      4. ONE of the following:
        1. The prescriber has assessed the patient’s current medications and discontinued any medications known to exacerbate myasthenia gravis (e.g., beta blockers, procainamide, quinidine, magnesium, anti-programmed death receptor-1 monoclonal antibodies, hydroxychloroquine, aminoglycosides); OR
        2. The prescriber has provided clinical rationale indicating that discontinuation of the offending agent is not clinically appropriate [medical record documentation required]; AND 
      5. ONE of the following: 
        1. The patient has tried and had an inadequate response to at least ONE agent used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) [medical record documentation required]; OR 
        2. The patient has an intolerance or hypersensitivity to ONE agent used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) [medical record documentation required]; OR 
        3. The patient has an FDA labeled contraindication to ALL agents used for the treatment of myasthenia gravis (i.e., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide) [medical record documentation required]; OR
        4. The patient required chronic intravenous immunoglobulin (IVIG) (i.e., at least every 3 months over 12 months without symptom control) [medical record documentation required]; OR 
        5. The patient required chronic plasmapheresis/plasma exchange (i.e., at least every 3 months over 12 months without symptom control) [medical record documentation required]; OR
  4. The patient has a diagnosis of neuromyelitis optica spectrum disorder (NMOSD) [medical record documentation required]; AND 
    1. The patient is 18 years of age or older; AND
    2. The patient weighs at least 40 kg [medical record documentation required]; AND 
    3. The patient is anti-aquaporin-4 (AQP4) antibody positive [medical record documentation required, including lab test]; AND
    4. The diagnosis has been confirmed by the presence of at least ONE of the following core clinical characteristics [medical record documentation required]:
      1. Optic neuritis; OR 
      2. Acute myelitis; OR
      3. Area postrema syndrome: Episode of otherwise unexplained hiccups or nausea and vomiting; OR
      4. Acute brainstem syndrome; OR 
      5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions; OR 
      6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions; AND 
    5. The patient has had at least ONE attack or relapse in the last 12 months prior to treatment with an immunotherapy or complement inhibitor for NMOSD (e.g., eculizumab, inebilizumab, satralizumab) [medical record documentation required]; AND
    6. The patient does NOT have any other alternative diagnoses to explain or cause the current disease symptoms (e.g., multiple sclerosis, ischemic optic neuropathy) [medical record documentation required]; AND
    7. The patient does NOT have evidence of an active meningococcal infection [medical record documentation required]; AND
    8. The patient will NOT be using the requested agent in combination with another biologic immunomodulator agent used to treat NMOSD (e.g., eculizumab, inebilizumab, satralizumab) [medical record documentation required]; AND 
  5. The patient is revaccinated according to current medical guidelines for vaccine use while on therapy with the requested agent; AND
  6. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
  7. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 180 days (6 months)

Continuation Criteria for Approval: 

  1. The patient was approved through Blue Cross NC initial criteria for approval; OR 
  2. The patient would have met initial criteria for approval at the time they started therapy [medical record documentation required]; AND 
  3. For patients with a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH):
    1. The patient has had either stabilization or improvement of symptoms from baseline while using the requested agent, as demonstrated by the following [medical record documentation required]: 
      1. Significant reduction in transfusion requirements [medical record documentation required]; AND
      2. No thromboembolism events persisting while using the requested agent [medical record documentation required]; AND 
    2. The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat PNH (e.g., eculizumab, iptacopan, pegcetacoplan) [medical record documentation required]; OR 
  4. For patients with a diagnosis of atypical hemolytic uremic syndrome (aHUS):
    1. The patient has demonstrated a positive clinical response as measured by hematological parameters or thrombotic microangiopathy (TMA) response while using the requested agent [medical record documentation required]; AND 
    2.  The patient will NOT be using the requested agent in combination with another complement inhibitor used to treat aHUS (e.g., eculizumab) [medical record documentation required]; OR
  5. For patients with a diagnosis of generalized myasthenia gravis (gMG):
    1. The patient has demonstrated clinical benefit with the requested agent (e.g., improved MG-ADL total score, improved quantitative myasthenia gravis total score) [medical record documentation required]; OR
  6. For patients with a diagnosis of neuromyelitis optica spectrum disorder (NMOSD):
    1. The patient has had a positive clinical response while using the requested agent, as demonstrated by disease stabilization or improvement (e.g., reduced number of relapses, improvement or stabilization of vision or paralysis) [medical record documentation required]; AND 
    2. The patient will NOT be using the requested agent in combination with another biologic immunomodulator agent used to treat NMOSD (e.g., eculizumab, inebilizumab, satralizumab) [medical record documentation required]; AND 
  7. The patient is revaccinated according to current medical guidelines for vaccine use while on therapy with the requested agent; AND
  8. The requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below); AND
  9. For requests for injection or infusion administration of the requested medication in an inpatient or outpatient hospital setting, Site of Care Criteria applies (outlined below)*

Duration of Approval: 365 days (1 year)

FDA Label Reference

MedicationIndicationDosing1HCPCSMaximum Units Allowed for Duration of Approval
ravulizumab-cwvz (Ultomiris® ) intravenous (IV) infusion

PNH in patients ≥1 month old weighing ≥5 kg

aHUS in patients ≥1 month old weighing ≥5 kg

gMG or NMOSD in adults weighing ≥40 kg

Loading and maintenance dosing are weight-based and maintenance doses (MD) are to start 2 weeks after loading dose (LD) at the following regimen:

5 to < 10 kg: 600 mg LD followed by MD of 300 mg every 4 weeks

10 to < 20 kg: 600 mg LD followed by MD of 600 mg every 4 weeks

20 to < 30 kg: 900 mg LD followed by MD of 2,100 mg every 8 weeks

30 to < 40 kg: 1,200 mg LD followed by MD of 2,700 mg every 8 weeks

40 to < 60 kg: 2,400 mg LD followed by MD of 3,000 mg every 8 weeks

60 to < 100 kg: 2,700 mg LD followed by MD of 3,300 mg every 8 weeks

≥100 kg: 3,000 mg LD followed by MD of 3,600 mg every 8 weeks

For patients currently treated with eculizumab, LD should be administered at time of next scheduled eculizumab dose.

 Loading and maintenance dosing are weight-based and maintenance doses (MD) are to start 2 weeks after loading dose (LD) at the following regimen:

40 to < 60 kg: 2,400 mg LD followed by MD of 3,000 mg every 8 weeks

60 to < 100 kg: 2,700 mg LD followed by MD of 3,300 mg every 8 weeks

≥100 kg: 3,000 mg LD followed by MD of 3,600 mg every 8 weeks

For patients currently treated with eculizumab, LD should be administered at time of next scheduled eculizumab dose.

J1303

Initial: 1,590

Continuation: 2,310

Site of Care Medical Necessity Criteria

  1. For requests for injection or infusion administration in an inpatient setting, the injection or infusion may be given if the above medical necessity criteria are met AND the inpatient admission is NOT for the sole purpose of administering the injection or infusion; OR 
  2. For requests for injection or infusion administration in an outpatient hospital setting, the injection or infusion may be given if the above medical necessity criteria are met AND ONE of the following must be met:
    1. History of mild adverse events that have not been successfully managed through mild pre-medication (e.g., diphenhydramine, acetaminophen, steroids, fluids, etc.); OR 
    2. Inability to physically and cognitively adhere to the treatment schedule and regimen complexity; OR 
    3. New to therapy, defined as initial injection or infusion OR less than 3 months since initial injection or infusion; OR 
    4. Re-initiation of therapy, defined as ONE of the following: 
      1. First injection or infusion after 6 months of no injections or infusions for drugs with an approved dosing interval less than 6 months duration; OR
      2. First injection or infusion after at least a 1-month gap in therapy outside of the approved dosing interval for drugs requiring every 6 months dosing duration; OR
    5. Requirement of a change in the requested restricted product formulation; AND
  3. If the Site of Care Medical Necessity Criteria in #1 or #2 above are not met, the injection or infusion will be administered in a home-based infusion or physician office setting with or without supervision by a certified healthcare professional.

References:

all information referenced is from FDA package insert unless otherwise noted below. 

  1. Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry Part B (Clinical Cytometry) 2010;78B:211-230.
  2. Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549.
  3. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naïve to complement inhibitore: the 301 study. Blood. 2019;133(6):530-539.
  4. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699- 3709. 
  5. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85:177. 

Policy Implementation/Update Information:

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

December 2024: Criteria change: For NMOSD indication: Removed criteria restricting use in patients previously treated with a complement inhibitor; further defined 2015 international consensus diagnostic criteria (core clinical characteristics and exclusion of alternative diagnoses) for clarity; removed expanded disability status score requirement, requirement of no HIV infection and no prior IVIG use within 3 weeks for clarity; adjusted continuation criteria to allow for positive clinical response while using the requested agent, as demonstrated by disease stabilization or improvement; and reordered criteria formatting and made other minor clarifications throughout criteria according to FDA label. Other minor formatting changes made throughout policy and dosing table for clarity with no change to intent.

April 2024: Criteria change: Added new indication for neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive with corresponding criteria and dosing table updates.

January 2024: Criteria update: For PNH indication, updated list of complement inhibitors not to be used concomitantly for clarity.

June 2022: Criteria change: Added new indication for generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody-positive with corresponding criteria and dosing table updates.

June 2021: Criteria change: Expanded PNH indication criteria and dosing table to age one month or older.

June 2021: Criteria change: Added to continuation section no concurrent use with another complement inhibitor and revaccination requirement according to guidelines; PNH: defined symptom stabilization or improvement within continuation section; added maximum units; medical policy formatting change. Policy notification given 4/16/2021 for effective date 6/16/2021.

*Further historical criteria changes and updates available upon request from Medical Policy and/or Corporate Pharmacy

Disclosures:

  1. Refer to package insert for full dosing details

Blue Cross and Blue Shield of North Carolina does not discriminate on the basis of race, color, national origin, sex, age or disability in its health programs and activities. Learn more about our non-discrimination policy and no-cost services available to you.

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