Blue Cross Blue Shield of Minnesota Medical Policy

 
 

Medical Policy:
II-196-009
Topic:
Eculizumab
Section:
Medicine
Effective Date:
May 31, 2021
Issued Date:
May 31, 2021
Last Revision Date:
March 2021
Annual Review:
March 2021
 
 

This policy version was replaced on March 28, 2022. To find the newest version, go to https://www.bluecrossmn.com/providers/medical-policy-and-utilization-management, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Eculizumab is a recombinant, humanized monoclonal antibody that binds to the complement protein C5, thereby inhibiting its break down into C5a and C5b and preventing generation of the terminal complement complex C5b-9. It can inhibit terminal complement-mediated intravascular hemolysis and complement-mediated thrombotic microangiopathy. Eculizumab is administered by intravenous infusion.

The U.S. Food and Drug Administration (FDA) has approved eculizumab (Soliris®) for treatment of patients with the following indications:

  • Paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis
  • Atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy
  • Generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AchR) antibody positive
  • Neuromyelitis optica spectrum disorder (NMOSD) in adults who are anti-aquaporin-4 (AQP4) antibody positive

Serious adverse reactions have occurred in patients receiving eculizumab, including life-threatening and fatal meningococcal infections. Due to these safety concerns, the FDA regulates eculizumab through a restricted distribution program under a risk evaluation and mitigation strategy (REMS) called the Soliris REMS Program. Under the REMS, prescribers must enroll in the program. The prescribing information for eculizumab also includes a black box warning.

Definitions

Myasthenia Gravis Foundation of America (MGFA) Clinical Classification:

  • 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.
  • Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.
  • Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular muscle weakness of any severity.
  • 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 IV.
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member's benefit plan.

I.   Initial Review for Eculizumab (Soliris®)

Eculizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

  • Diagnosis of ONE of the following:
    • Paroxysmal nocturnal hemoglobinuria (PNH) AND ALL the following:
      • Confirmation of PNH by flow cytometry, including detection of PNH clones (i.e., PNH type III red cells or glycosylphosphatidylinositol-anchored proteins [GPI-AP]-deficient polymorphonuclear cells); AND
      • ONE of the following:
        • Patient is transfusion dependent (defined as hemoglobin ≤7 g/dL OR hemoglobin ≤9 g/dL in patients with symptoms of anemia); or
        • Patient has high lactate dehydrogenase activity (defined as ≥1.5 times the upper limit of normal);
        • Presence of organ damage secondary to chronic hemolysis; or
        • Patient is pregnant and potential benefit outweighs potential fetal risk; or
        • Documented history of a major adverse vascular event from thromboembolism; OR
    • Atypical hemolytic uremic syndrome (aHUS) AND ALL the following:
      • Shiga toxin-producing E. coli-related hemolytic uremic syndrome (STEC-HUS) has been ruled out (e.g., negative for STEC infection); AND
      • Thrombotic thrombocytopenic purpura (TTP) has been ruled out (e.g., normal ADAMTS-13 activity and no evidence of an ADAMTS-13 inhibitor), or if TTP cannot be ruled out by laboratory and clinical evaluation, a trial of plasma exchange did not result in clinical improvement; OR
    • Generalized myasthenia gravis (gMG) AND ALL the following:
      • Age 18 years or older; AND
      • Positive serological test for anti-acetylcholine receptor (AchR) antibodies; AND
      • Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV; AND
      • Myasthenia Gravis Activities of Daily Living (MG-ADL) total score ≥6; AND
      • ONE of the following:
        • Patient has tried and failed pyridostigmine; or
        • Documented intolerance, FDA labeled contraindication, or hypersensitivity to pyridostigmine; AND
      • Patient has tried and failed treatment within the past 12 months with ONE of the following:
        • At least 2 or more immunosuppressive therapies (e.g., azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide, corticosteroids) either in combination or as monotherapy; OR
        • At least 1 immunosuppressive therapy (e.g., azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, methotrexate, cyclophosphamide, corticosteroids) and ONE of the following:
          • Chronic intravenous immunoglobulin (IVIG); or
          • Plasmapheresis/plasma exchange given at least weekly for a minimum of 4 weeks without symptom control; OR
        • Documented intolerance, FDA labeled contraindication, or hypersensitivity to immunosuppressive therapies, IVIG, and plasmapheresis/plasma exchange;
    • OR
    • Neuromyelitis optica spectrum disorder (NMOSD) AND ALL the following:
      • Age 18 years or older; AND
      • Positive serological test for aquaporin-4 (AQP4) antibodies; AND
      • Clinical characteristics of NMOSD (e.g., optic neuritis, acute myelitis); AND
      • ONE of the following: 
        • History of at least 2 relapses during the previous 12 months prior to initiating eculizumab; or
        • History of at least 3 relapses during the previous 24 months, at least one relapse occurring within the past 12 months prior to initiating eculizumab; 
      • AND
      • ONE of the following: 
        • Previously tried and failed satralizumab (Enspryng™); OR
        • Documented intolerance, FDA labeled contraindication, or hypersensitivity to satralizumab (Enspryng™); 
      • AND
      • Expanded Disability Status Scale (EDSS) score ≤7.0; AND
      • Not receiving eculizumab in combination with disease modifying therapies for treatment of multiple sclerosis (e.g., beta interferons [Avonex®], fingolimod [Gilenya®], dimethyl fumarate [Tecfidera®]);
  • AND
  • Eculizumab is prescribed by or in consultation with a specialist in the patient’s disease; AND
  • Eculizumab will not be used in combination with ravulizimab (Ultomiris™); or other biologic immunomodulators (e.g. rituximab); AND
  • Patient has been immunized with a meningococcal vaccine at least 2 weeks prior to administration of the first dose of eculizumab (unless the clinical record documents that the risks of delaying eculizumab outweigh the risk of meningococcal infection); AND
  • No evidence of an active meningococcal infection; AND
  • No FDA labeled contraindications to eculizumab (see table 1 below); AND
  • The dose is within the FDA labeled dose (see table 2 below); AND
  • For commercial health plan members only, eculizumab is administered in accordance with site of service criteria (see policy XI-06); AND
  • For commercial health plan members only, step therapy supplement criteria may apply for select conditions (see policy II-242: Step Therapy Supplement).

II.  Renewal Review for Eculizumab (Soliris®)

Eculizumab may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

  • Previously approved for eculizumab through the initial review process; AND
  • Demonstrated positive clinical response to eculizumab therapy. Examples include:
    • For patients with paroxysmal nocturnal hemoglobinuria (PNH), decreased requirement for transfusions, stabilization of hemoglobin, reduction of lactate dehydrogenase (LDH), stabilization and/or slowing of disease progression;
    • For patients with atypical hemolytic uremic syndrome (aHUS), improved platelet count, reduction of lactate dehydrogenase (LDH), improved renal function, stabilization and/or slowing of disease progression;
    • For patients with generalized myasthenia gravis (gMG), improved MG-ADL total score, quantitative myasthenia gravis total score, stabilization and/or slowing of disease progression; 
    • For patients with neuromyelitis optic spectrum disorder (NMOSD), reduced rates of relapses, improvement or stabilization of vision or paralysis, stabilization and/or slowing of disease progression;
  • AND
  • Eculizumab is prescribed by or in consultation with a specialist in the patient’s disease; AND
  • Eculizumab will not be used in combination with ravulizumab (Ultomiris™) or other biologic immunomodulators (e.g. rituximab); AND
  • No FDA labeled contraindications to eculizumab (see table 1 below).
  • The dose is within the FDA labeled dose (see table 2 below); AND
  • For commercial health plan members only, eculizumab is administered in accordance with site of service criteria (see policy XI-06).

III. Experimental/Investigative Uses

All other uses of eculizumab are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

J1300



Table 1. FDA Labeled Contraindications

Agent

FDA Labeled Contraindications

Eculizumab (Soliris®)

Patients with unresolved serious Neisseria meningitidis infection

Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying eculizumab treatment outweigh the risks of developing a meningococcal infection

 

Table 2. Dosing
NOTE: See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table.

FDA Labeled Indications

Dosing

Paroxysmal nocturnal hemoglobinuria (PNH)

Patients  ≥18 years: 600 mg weekly for the first 4 weeks, then 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter.

Atypical hemolytic uremic syndrome (aHUS)

Patients  ≥18 years: 900 mg weekly for 4 weeks, 1200 mg for fifth dose 1 week later, 1200 mg every 2 weeks thereafter.

For patients <18 years, administer based upon body weight:

Body Weight

Induction

Maintenance

5 kg to less than 10 kg

300 mg weekly for 1 week

300 mg at week 2; then 300 mg every 3 weeks

10 kg to less than 20 kg

600 mg weekly for 1 week

300 mg at week 2; then 300 mg every 2 weeks

20 kg to less than 30 kg

600 mg weekly for 2 weeks

600 mg at week 3; then 600 mg every 2 weeks

30 kg to less than 40 kg

600 mg weekly for 2 weeks

900 mg at week 3; then 900 mg every 2 weeks

≤40 kg

900 mg weekly for 4 weeks

1200 mg at week 5; then 1200 mg every 2 weeks

 

Generalized myasthenia gravis (gMG)

900 mg weekly for 4 weeks, then 1200 mg for fifth dose 1 week later, then 1200 mg every 2 weeks thereafter.

Neuromyelitis optica spectrum disorder (NMOSD)

900 mg weekly for 4 weeks, then 1200 mg for fifth dose 1 week later, then 1200 mg every 2 weeks thereafter.


Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization. In addition, the following documentation must also be submitted:

Initial Review

  1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
  2. If treating myasthenia gravis, clinical notes describing current and past medications for the diagnosis, including response to the medications.
  3. The dose being requested, including the patient's weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
  4. For commercial health plan members only, the site of service for eculizumab administration is specified, including CMS place of service code (see policy XI-06). If eculizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.
  5. For commercial health plan members only, when step therapy requirements apply for the requested indication, documentation for one or more of the step therapy supplement criteria MUST be provided (see policy II-242).

Renewal Review

  1. Documentation of prior approval for eculizumab through the initial review process.
  2. Documentation supporting positive clinical response (e.g., slowing of disease progression or decrease in symptom severity and/or frequency).
  3. The dose being requested, including the patient's weight if the diagnosis requires weight-based dosing. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
  4. For commercial health plan members only, the site of service for eculizumab administration is specified, including CMS place of service code (see policy XI-06). If eculizumab is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.



Denial Statements

No additional statements



Links





Blue Cross and Blue Shield of Minnesota medical policies apply generally to all Blue Cross and Blue Plus plans and products. Benefit plans vary in coverage and some plans may not provide coverage for certain services addressed in the medical policies. When determining coverage, reference the member’s specific benefit plan, including exclusions and limitations.

Medicaid products may provide different coverage for certain services, which may be addressed in different policies. For Minnesota Health Care Program (MHCP) policies, please consult the MHCP Provider Manual website.

Medicare products may provide different coverage for certain services, which may be addressed in different policies. For Medicare National Coverage Determinations (NCD), Local Coverage Determinations (LCD), and/or Local Coverage Articles, please consult CMS, National Government Services, or CGS websites. 

Note that services with specific coverage criteria may be reviewed retrospectively to determine if criteria are being met. Retrospective denial of claims may result if criteria are not met.

Blue Cross and Blue Shield of Minnesota reserves the right to revise, update and/or add to its medical policies at any time without notice. Codes listed on this policy are included for informational purposes only and are subject to change without notice. Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. 

These guidelines are the proprietary information of Blue Cross and Blue Shield of Minnesota. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

Acknowledgements:

CPT® codes copyright American Medical Association® 2022. All rights reserved.

CDT codes copyright American Dental Association® 2022. All rights reserved.