BlueCross BlueShield of Tennessee Medical Policy Manual

Eculizumab

NDC CODE(S)

25682-0001-XX - Soliris 10MG/ML Solution (ALEXION PHARMACEUTICALS)

DESCRIPTION

Eculizumab, a recombinant monoclonal antibody, binds to the complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the generation of terminal complement complex C5b-9. The complement system of proteins, which is part of the immune system, destroys abnormal red blood cells. Eculizumab prevents destruction of red blood cells that are deficient in terminal complement inhibitors.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL

*Important Note: Sensitivity of the AQP4-IgG antibodies laboratory test should be ≥ 77% (e.g., AQP4 FACS [M23 isoform]). With a negative or inconclusive result from a less sensitive test ONLY, at least two core clinical characteristics must be met, one being either optic neuritis, acute myelitis with longitudinally extensive transverse myelitis lesions or area postrema syndrome with additional MRI requirements (see chart below).  After meeting these requirements, a diagnosis of NMOSD for the use of eculizumab can be confirmed.

        • History of minimum of 2 relapses in the last 12 months OR 3 relapses in the last 24 months, with at least 1 relapse in the last 12 months

        • Expanded Disability Status Score (EDSS) of ≤ 7.0 (consistent with the presence of at least limited ambulation with aid

        • Individual is receiving concurrent corticosteroid therapy of 20 mg per day or less and those receiving immunosuppressive therapy (e.g. azathioprine, glucocorticoids, mycophenolate, etc) are on a stable dose regimen

        • Individual has/will ALL of the following

          • NOT received therapy with rituximab or mitoxantrone in the last 3 months

          • NOT received intravenous immune globulin (IVIG) in the last 3 weeks

          • NOT concomitantly receive therapy with ANY ONE of the following:

            • IL6-inhibitor (e.g., satralizumab)

            • Anti-CD20-directed antibody (e.g., rituximab)

            • Anti-CD19-directed antibody (e.g., inebilizumab)

      • Paroxysmal nocturnal hemoglobinuria (PNH) diagnosis with ALL of the following:

        • Individual is 18 years of age or older

        • Diagnosis must be accompanied by detection of PNH clones of at least 10% by flow cytometry diagnostic testing

        • Demonstrate the presence of at least 2 different GPI protein (glycosylphosphatidylinositol) deficiencies (e.g., CD55, CD59, etc.) within at least 2 different cell lines (granulocytes, monocytes, erythrocytes)

        • Individual has ANY ONE of the following indications for therapy:

          • Presence of a thrombotic event

          • Presence of organ damage secondary to chronic hemolysis

          • Individual is pregnant and potential benefit outweighs potential fetal risk

          • Is transfusion dependent

          • High LDH activity (defined as ≥1.5 x ULN) with clinical symptoms

        • Documented baseline values for ANY ONE or more of the following (necessary for renewal):

          • Serum lactate dehydrogenase (LDH)

          • Hemoglobin level

          • Packed RBC transfusion requirement

RENEWAL CRITERIA

INDICATION(S)

DOSAGE & ADMINISTRATION

(Doses should be administered at the following intervals or within two days of these time points)

Paroxysmal nocturnal hemoglobinuria

Loading dose:

600mg every 7 days for the first 4 weeks, followed by 900mg for the fifth dose 7 days later and then 900mg every 14 days thereafter (initial loading dose requires a total of 3,300mg over 5 weeks)

 

Maintenance dose:

900 mg every 14 days

Atypical hemolytic uremic syndrome

ADULTS

Loading dose:

900 mg intravenously every 7 days for the first 4 weeks, followed by 1,200mg for the fifth dose 7 days later and then 1,200mg every 14 days thereafter (initial loading dose requires a total of 4,800mg over 5 weeks)

 

Maintenance dose:

1200 mg intravenously every 14 days

 

Pediatric < 18 years:

5 kg to <10 kg - 300 mg weekly x 1 dose, 300 mg at week 2, then 300 mg every 3 weeks

10 kg to <20 kg - 600 mg weekly x 1 dose, 300 mg at week 2, then 300 mg every 2 weeks

20 kg to <30 kg - 600 mg weekly x 2 doses, 600 mg at week 3, then 600 mg every 2 weeks

30 kg to <40 kg - 600 mg weekly x 2 doses, 900 mg at week 3, then 900 mg every 2 weeks

≥ 40 kg - 900 mg weekly x 4 doses, 1200 mg at week 5, then 1200 mg every 2 weeks

Generalized Myasthenia Gravis (gMG) and

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Loading dose:

900 mg intravenously every 7 days for the first 4 weeks, followed by 1,200 mg intravenously for the fifth dose 7 days later

 

Maintenance dose:

1200 mg intravenously every 14 days

Dose Adjustment for aHUS (adult and pediatric patients), gMG (adult patients) and NMOSD (adult patients) in Case of Plasmapheresis, Plasma Exchange or Fresh Frozen Plasma Infusion

Type of Plasma Exchange

Most Recent Eculizumab Dose

Supplemental Eculizumab With Each Plasma Intervention

Timing of Supplemental Eculizumab Dose

Plasmapheresis or plasma exchange (PE)

300 mg

300 mg per each plasmapheresis or PE

Within 60 minutes after each plasmapheresis or PE

≥ 600 mg

600 mg per each plasmapheresis or PE

Fresh frozen plasma infusion (FFP)

≥300 mg

300 mg per each infusion of FFP

60 minutes prior to each infusion of FFP

LENGTH OF AUTHORIZATION

Coverage will be provided for twelve months for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) and may be renewed.

For Generalized Myasthenia Gravis and Neuromyelitis Optica Spectrum Disorder, initial coverage will be provided for 6 months and may be renewed annually thereafter.

Refer to DOSAGE LIMITS below

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES

Centers for Disease Control and Prevention. (2015, June). Morbidity and Mortality Weekly Report. Use of serogroup B meningococcal vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2015. Retrieved February 23, 2016 from http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6422a3.htm.

Laurence, J., Haller, H., Mannucci, P. M., Nangaku, M., Praga, M., Rodriguez de Cordoba, S. (2016). Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis. Clinical Advances in Hematology and Oncology, 14 Suppl, 11(11), 2-15. Abstract retrieved March 13, 2018 from PubMed database.

Lexi-Comp Online. (2019, June). AHFS DI. Eculizumab. Retrieved August 15, 2019 from Lexi-Comp Online with AHFS.

Mayo Clinic Laboratories. (2019). Test Definition: NMOFS - NMO/AQP4 FACS, S. Mayo Foundation for Medical Education and Research. Retrieved September 19, 2019 from https://www.mayocliniclabs.com/test-catalog/download-setup.php?format=pdf&unit_code=38324.

MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2020, August). Eculizumab. Retrieved November 24, 2020 from MICROMEDEX Healthcare Series.

Noris, M., Bresin, E., Mele, C., Remuzzi, G. (2007, March, updated 2016, June). Genetic Atypical Hemolytic-Uremic Syndrome. In: Adam, M. P., Ardinger, H. H., Pagon, R.A., et al., eds., GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Retrieved October 29, 2018 from https://www.ncbi.nlm.nih.gov/books/NBK1367/.

Parker, C. J. (2016, December).American Society of Hematology Education Program. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology. v Dec 2; 2016(1), 208–216. Retrieved October 29, 2018 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142517/.

U. S. Food and Drug Administration. (2020, November). Center for Drug Evaluation and Research. Soliris® (eculizumab). Retrieved November 23, 2020 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125166s434lbl.pdf.   

Wingerchuk, D. M., Banwell, B., Bennett, J. L., Cabre, P., Carroll, W., Chitnis, T., et al. (2015). International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015(85), 177 – 189.

Wingerchuk, D. M., Lennon, V.A., Pittock, S.J., Lucchinetti, C.F., Weinshenker, B.G. (2006). Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006(66), 1485 -1489.urology. 2015(85), 177 – 189.

Wingerchuk, D. M., Lennon, V.A., Pittock, S.J., Lucchinetti, C.F., Weinshenker, B.G. (2006). Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006(66), 1485 -1489.

ORIGINAL EFFECTIVE DATE:  2/14/2016

MOST RECENT REVIEW DATE:    4/2/2021

ID_MRx

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information

 

 

DOSAGE LIMITS

Maximum billable units per dose and over time by indication as a Medical Benefit; 1 billable unit = 10 mg

DIAGNOSIS

LOADING DOSES

MAINTENANCE DOSE

PNH

60 billable units Days 1, 8, 15, & 22; then 90 billable units Day 29

90 billable units every 14 days

aHUS, gMG, NMOSD

90 billable units Days 1, 8, 15, & 22; then 120 billable units Day 29

120 billable units every 14 days