Clinical Policy: Canakinumab (Ilaris) Form

CENTENE Corporation

Clinical Policy: Canakinumab (Ilaris) Reference Number: CP.PHAR.246 Effective Date: 08.01.16 Last Review Date: 05.26 Line of Business: Commercial, HIM/ICHRA, Medicaid Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description Canakinumab (Ilaris®) is an interleukin-1 blocker.

FDA Approved Indication(s) Ilaris is indicated for the treatment of:

• Periodic fever syndromes: ○ Cryopyrin-associated periodic syndromes (CAPS) in adults and children 4 years of age and older including:
  • ■ Familial cold autoinflammatory syndrome (FCAS)
  • ■ Muckle-Wells syndrome (MWS). ○ Tumor necrosis factor receptor associated periodic syndrome (TRAPS) in adult and pediatric patients ○ Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) in adult and pediatric patients ○ Familial Mediterranean fever (FMF) in adult and pediatric patients
• Active Still’s disease, including adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older
• Gout flares in adults in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate

Approval duration: Medicaid/HIM/ICHRA – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

Approval duration: Medicaid/HIM/ICHRA – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

Approval duration: Medicaid/HIM/ICHRA – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

Approval duration: 3 months

E. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid, or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

Medicaid/HIM/ICHRA – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer

Approval duration: Medicaid/HIM/ICHRA – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer

C. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid, or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant

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 line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance
 marketplace/ICHRA, and CP.PMN.53 for Medicaid.

III.Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid or evidence of coverage documents; B. Combination use with biological disease-modifying antirheumatic drugs (bDMARDs) or potent immunosuppressants, including but not limited to any tumor necrosis factor (TNF) antagonists [e.g., Cimzia®, Enbrel®, Humira® and its biosimilars, Remicade® and its biosimilars, Simponi®, Otezla®], interleukin agents [e.g., Actemra® (IL-6RA) and its biosimilars, Arcalyst® (IL-1 blocker), Bimzelx® (IL-17A and F antagonist), Cosentyx® (IL-17A inhibitor), Ilaris® (IL-1 blocker), Ilumya® (IL-23 inhibitor), Kevzara® (IL- 6RA), Kineret® (IL-1RA), Omvoh™ (IL-23 antagonist), Siliq® (IL-17RA), Skyrizi™ (IL- 23 inhibitor), Spevigo® (IL-36 antagonist), Stelara® (IL-12/23 inhibitor) and its biosimilars, Taltz® (IL-17A inhibitor), Tremfya® (IL-23 inhibitor)], Janus kinase inhibitors (JAKi) [e.g., Cibinqo™, Olumiant™, Rinvoq™, Xeljanz®/Xeljanz® XR,], anti- CD20 monoclonal antibodies [Rituxan® and its biosimilars], selective co-stimulation modulators [Orencia®], integrin receptor antagonists [Entyvio®], tyrosine kinase 2 inhibitors [Sotyktu™], and sphingosine 1-phosphate receptor modulator [Velsipity™] because of the additive immunosuppression, increased risk of neutropenia, as well as increased risk of serious infections.

IV.Appendices/General Information Appendix A: Abbreviation/Acronym Key AOSD: adult-onset Still’s disease CAPS: cryopyrin-associated periodic

  syndromes

FCAS: familial cold autoinflammatory

  syndrome

FDA: Food and Drug Administration FMF: familial Mediterranean fever GI: gastrointestinal HIDS: hyperimmunoglobulin D

  syndrome

JAKi: Janus kinase inhibitors MKD: mevalonate kinase deficiency MTX: methotrexate MWS: Muckle-Wells syndrome NSAID: non-steroidal anti-inflammatory

  drugs

SJIA: systemic juvenile idiopathic arthritis TRAPS: tumor necrosis factor receptor

   associated periodic syndrome

Appendix B: Therapeutic Alternatives This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

| Drug Name | Dosing Regimen | Dose Limit/

Maximum Dose |

|-----------|---------------|----------------|

| colchicine

(Colcrys®) | FMF PO in 1-2 divided doses based on age: Age 4– 6 years: 0.3-1.8 mg/day | FMF 2.4 mg/day |

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| Drug Name | Dosing Regimen | Dose Limit/

Maximum Dose |

|-----------|---------------|----------------|

| | Age 6 – 12 years: 0.9-1.8 mg/day

Age > 12 years: 1.2-2.4 mg/day Gout flare 1.2 mg at first sign of flare, followed by 0.6 mg one hour later | Gout flare 1.8 mg/treatment |

| corticosteroids

(e.g., prednisone, methylprednisolone) | SJIA 0.5 – 2 mg/kg/day PO of prednisone or equivalent AOSD Varies Gout flare Varies | Varies |

| leflunomide

(Arava®) | SJIA* 10 – 19.9 kg:10 mg PO QD 20- 40 kg: 15 mg PO QD ≥ 40 kg: 20 mg PO QD | 20 mg/day |

| methotrexate

(Trexall®, Otrexup®TM, Rasuvo®, RediTrex®, Xatmep®TM, Rheumatrex®) | SJIA* 0.5 – 1 mg/kg/week PO or SC | 30 mg/week |

| NSAIDs (e.g.,

naproxen, ibuprofen, indomethacin) | AOSD, Gout flare, sJIA Varies | Varies |

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label

Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): confirmed hypersensitivity to the active substance or to any of the excipients.
• Boxed warning(s): none reported

Appendix D: General Information

• Periodic fever syndromes are a group of rare autoinflammatory diseases that include cryopyrin-associated periodic syndromes (CAPS), tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), and familial Mediterranean fever (FMF). Diagnosis of these diseases can be confirmed by genetic testing.
• Three related conditions make up the broader disease known as CAPS: familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal- onset multisystem inflammatory disease (NOMID), also known as chronic infantile

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neurologic cutaneous articular syndrome (CINCA). While Ilaris is FDA-approved for FCAS and MWS, it is not FDA-approved for use in patients with NOMID/CINCA.

• Ilaris is the first therapeutic option for TRAPS and HIDS/MKD and the first biologic option for FMF. In FMF, the current standard of care is colchicine, a relatively safe oral therapy indicated in patients ages 4 and up. Colchicine has well-established benefit in FMF and has been used for decades. Although no United States clinical practice guidelines exist for TRAPS, HIDS/MKD, and FMF, the European League Against Rheumatism (EULAR) guidelines for the management of FMF recommend colchicine be initiated at diagnosis for all patients and response to therapy be assessed every 6 months.
• Examples of positive response to therapy: ○ Periodic fever syndromes (FCAS, MWS, TRAPS, HIDS/MKD, and FMF) include reduction/normalization of: C-reactive protein (CRP) levels, serum amyloid A (SAA) levels, flare frequency, or severity and duration of symptoms (e.g., joint pain, rash, fever/chills, eye pain, fatigue). ○ SJIA include improvement in: quantitative measures such as physician global assessment of disease activity, parent or patient global assessment of well-being, number of joints with active arthritis, number of joints with limited range of motion, CRP, and functional ability (CHAQ). ○ AOSD include normalization or improvement in laboratory test results for serum markers of inflammation (e.g., ESR or CRP), sustained improvement in member’s symptoms and disease stability. Chart notes indicating improvement in rash, joint pain and/or swelling and fevers.
• Failure of a trial of conventional DMARDs: ○ Child-bearing age is not considered a contraindication for use of MTX. Each drug has risks in pregnancy. An educated patient and family planning would allow use of MTX in patients who have no intention of immediate pregnancy. ○ Social use of alcohol is not considered a contraindication for use of MTX. MTX may only be contraindicated if patients choose to drink over 14 units of alcohol per week. However, excessive alcohol drinking can lead to worsening of the condition, so patients who are serious about clinical response to therapy should refrain from excessive alcohol consumption.
• For acute gout flares: Examples where repeated corticosteroids are not appropriate may include, but are not limited to the following: osteoporosis, osteonecrosis, Cushing syndrome, diabetes mellitus, myopathy, glaucoma, congestive heart failure, or peptic ulcer disease.

V. Dosage and Administration

Weight ≥ 15 kg to ≤ 40 kg: 2 mg/kg SC every 8 weeks (if inadequate response, may increase to 3 mg/kg) | 150 mg/8 weeks |

| CAPS (TRAPS,

HIDS/MKD, FMF) | Weight > 40 kg: 150 mg SC every 4 weeks (if inadequate response, may increase to 300 mg every 4 weeks) | 300 mg/4 weeks |

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(if inadequate response, may increase to 4 mg/kg) | |

| SJIA, AOSD | Weight ≥ 7.5 kg: 4 mg/kg SC (up to a

maximum of 300 mg) every 4 weeks | 300 mg/4 weeks |

| Treatment of gout

flares | 150 mg SC (interval of at least 12 weeks before a new dose) | 150 mg/ 12 weeks |

VI. Product Availability Single-dose vial for injection, solution: 150 mg/mL

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions.

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services.

Note: For Medicaid members, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

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CLINICAL POLICY Canakinumab

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