Subject: Soliris (eculizumab)

Drug

Soliris®  (eculizumab)

Policy:

Note: The provision of physician samples does not guarantee coverage under the provisions of the pharmacy benefit. All criteria below must be met in order to obtain coverage of Soliris (eculizumab). 

Site of Care Utilization Management Policy applies.  For information on site of service for Soliris (eculizumab), see Utilization Management Policy on Site of Care for Specialty Drug Infusions at https://www.aetna.com/health-care-professionals/utilization-management/drug-infusion-site-of-care-policy.html.   

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Soliris (eculizumab) is subject to precertification. If precertification requirements apply Aetna considers this drug to be medically necessary for those members who meet the following precertification criteria: 

I. INDICATIONS 

The indications below including FDA-approved indications and compendial uses are considered covered benefits provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy.

FDA-Approved Indications¹

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

Limitations of Use: Soliris is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).

All other indications are considered experimental/investigational and not medically necessary.

 

II. REQUIRED DOCUMENTATION

Submission of the following information is necessary to initiate the prior authorization review for new requests for treatment of:

1. Atypical hemolytic uremic syndrome: ADAMTS 13 level
2. Paroxysmal nocturnal hemoglobinuria: flow cytometry used to show results of GPI-APs deficiency
3. Generalized myasthenia gravis: anti-acetylcholine receptor (AchR) antibody positive, clinical classification of myasthenia gravis score, MG activities of daily living score, use of IVIG and rituximab, use of two immunosuppressive therapies
4. Neuromyelitis optica spectrum disorder: immunoassay used to confirm anti-aquaporin-4 (AQP4) antibody is present

 

III. CRITERIA FOR INITIAL APPROVAL

1. Atypical hemolytic uremic syndrome^1,2
   Authorization of 6 months may be granted for treatment of atypical hemolytic uremic syndrome not caused by Shiga toxin when all of the following criteria are met:
1. ADAMTS 13 activity level above 5%
2. Absence of Shiga toxin
   
   
2. Paroxysmal nocturnal hemoglobinuria^1,3,8-10
   Authorization of 6 months may be granted for treatment of paroxysmal nocturnal hemoglobinuria (PNH) when all of the following criteria are met:
1. The diagnosis of PNH was confirmed by detecting a deficiency of glycosylphosphatidylinositol-anchored proteins (GPI-APs) as demonstrated by either of the following:
   1. At least 5% PNH cells
   2. At least 51% of GPI-anchored protein deficient poly-morphonuclear cells
2. Flow cytometry is used to demonstrate GPI-anchored proteins deficiency
   
   
3. Generalized myasthenia gravis (gMG) ^1,4
   Authorization of 6 months may be granted for treatment of generalized myasthenia gravis (gMG) when all of the following criteria are met:
1. Anti-acetylcholine receptor (AchR) antibody positive
2. Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV
3. MG activities of daily living (MG-ADL) total score ≥6
4. Meets both of the following:
1. Member has had an inadequate response to at least two immunosuppressive therapies listed below:
   1. azathioprine
   2. cyclosporine
   3. mycophenolate mofetil
   4. tacrolimus
   5. methotrexate
   6. cyclophosphamide
2. Member has inadequate response to chronic IVIG AND rituximab
   
   
4. Neuromyelitis Optica Spectrum Disorder (NMOSD)^1,12,13
   Authorization of 6 months may be granted for treatment of neuromyelitis optica spectrum disorder (NMOSD) when all of the following criteria are met:
1. Anti-aquaporin-4 (AQP4) antibody positive
2. Member exhibits one of the following core clinical characteristics of NMOSD:
   1. Optic neuritis
   2. Acute myelitis
   3. Area postrema syndrome (episode of otherwise unexplained hiccups or nausea and vomiting)
   4. Acute brainstem syndrome
   5. Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions
   6. Symptomatic cerebral syndrome with NMOSD-typical brain lesions
3. The member will not receive the requested drug concomitantly with other biologics for the treatment of NMOSD.
    

 

IV. CONTINUATION OF THERAPY   

1. Atypical hemolytic uremic syndrome^1,2
   Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and demonstrate a positive response to therapy (e.g., normalization of lactate dehydrogenase (LDH) levels, platelet counts).
   
   
2. Paroxysmal nocturnal hemoglobinuria^1,3
   Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and demonstrate a positive response to therapy (e.g., improvement in hemoglobin levels normalization of lactate dehydrogenase [LDH] levels).
   
   
3. Generalized myasthenia gravis (gMG) ¹
   Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when there is no evidence of unacceptable toxicity or disease progression while on the current regimen and demonstrate a positive response to therapy (e.g., improvement in MG-ADL score, changes compared to baseline in Quantitative Myasthenia Gravis (QMG) total score).
   
   
4. Neuromyelitis optica spectrum disorder (NMOSD)^1,12
   Authorization of 12 months may be granted for continued treatment in members requesting reauthorization when all of the following criteria are met:
   There is no evidence of unacceptable toxicity or disease progression while on the current regimen.
   The member demonstrates a positive response to therapy (e.g., reduction in number of relapses).
   The member will not receive the requested drug concomitantly with other biologics for the treatment of NMOSD.

 

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. Soliris [package insert]. New Haven, CT: Alexion Pharmaceuticals, Inc.; June 2019.
2. Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. Published online: April 11, 2015.
3. Parker CJ. Management of paroxysmal nocturnal hemoglobulinuria in the era of complement inhibitory therapy. Hematology. 2011; 21-29.
4. Sanders D, Wolfe G, Benatar M et al. International consensus guidance for management of myasthenia gravis. Neurology. 2016; 87 (4):419-425.
5. Jaretzki A, Barohn RJ, Ernstoff RM et al. Myasthenia Gravis: Recommendations for Clinical Research Standards. Ann Thorac Surg. 2000;70: 327-34.
6. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. NEJM. 2006;335:1233-43.
7. Howard JF, Utsugisawa K, Benatar M. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (REGAIN); a phase 3, randomized, double-blind, placebo-controlled, multicenter study. Lancet Neurol. 2017 Oct 20. http://dx.doi.org/10.1016/S1474-4422(17)30369-1Ingenix HCPCS Level II, Expert 2011.
8. Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111(4):1840-1847.
9. Borowitz MJ, Craig F, DiGiuseppe JA, et al. Guidelines for the Diagnosis and Monitoring of Paroxysmal Nocturnal Hemoglobinuria and Related Disorders by Flow Cytometry. Cytometry B Clin Cytom. 2010: 78: 211-230.
10. Preis M, Lowrey CH. Laboratory tests for paroxysmal nocturnal hemoglobinuria (PNH). Am J Hematol. 2014;89(3):339-341.
11. Lee JW, Sicre de Fontbrune F, Wong LL, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: The 301 study. Blood. 2018 Dec 3; pii: blood-2018-09-876136.
12. Pittock SJ, Berthele A, Kim HJ, et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 May 3. doi: 10.1056/NEJMoA1900866.
13. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015; 85:177-189.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

April 6, 2021