OFEV, Nintedanib Esylate Form

Nintedanib (Ofev®) is a kinase inhibitor. FDA Approved Indication(s) Ofev is indicated: • For the treatment of idiopathic pulmonary fibrosis (IPF); • For the treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype; • To slow the rate of decline in pulmonary function in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Ofev is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Idiopathic Pulmonary Fibrosis (must meet all):

1. Diagnosis of IPF;
   2. Prescribed by or in consultation with a pulmonologist;
   3. Age ≥ 18 years;
   4. Member meets (a and b): a. Pulmonary fibrosis on high resolution computed tomography (HRCT) with one of the following (i or ii): i. Usual interstitial pneumonia (UIP) pattern; ii. Probable or indeterminate UIP pattern, and surgical lung biopsy or cellular analysis of bronchoalveolar lavage fluid confirms the diagnosis of IPF; b. Known causes of pulmonary fibrosis have been ruled out (see Appendix D);

2. Baseline forced vital capacity (FVC) ≥ 50% of predicted;

   6. Baseline carbon monoxide diffusing capacity (DLCO) ≥ 30% of predicted;
   7. Ofev is not prescribed concurrently with Esbriet®;
   8. Member is not an active smoker as evidenced by recent (within the last 30 days) negative nicotine metabolite (i.e., cotinine) test;
   9. Dose does not exceed 300 mg (2 capsules) per day.
      Approval duration: 6 months Page 1 of 8

   CLINICAL POLICY Nintedanib B. Chronic Fibrosing Interstitial Lung Disease (must meet all):

3. Diagnosis of one of the following chronic fibrosing ILD subtypes (a-g): a. Chronic fibrosing hypersensitivity pneumonitis; b. Autoimmune ILD (e.g., rheumatoid arthritis-related ILD); c. Mixed connective tissue disease-associated ILD; d. Idiopathic non-specific interstitial pneumonia; e. Unclassifiable idiopathic interstitial pneumonia; f. Environmental/occupational exposure-related ILD; g. Sarcoidosis;
4. Prescribed by or in consultation with a pulmonologist;
   3. Age ≥ 18 years;
   4. For new starts only: member meets both of the following within the past 24 months (a and b): a. Pulmonary fibrosis affecting > 10% of lung volume on HRCT; b. Documentation of one of the following (i or ii): i. A relative decline in the FVC of ≥ 10% of the predicted value; ii. A relative decline in the FVC of 5% to < 10% of the predicted value plus either worsening of respiratory symptoms or an increased extent of fibrosis on HRCT;
5. Baseline FVC ≥ 45% of predicted;
   6. Baseline DLCO ≥ 30% of predicted;
   7. Ofev is not prescribed concurrently with Esbriet;
   8. Member is not an active smoker as evidenced by recent (within the last 30 days) negative nicotine metabolite (i.e., cotinine) test;
   9. Dose does not exceed 300 mg (2 capsules) per day. Approval duration: 6 months C. Systemic Sclerosis Associated Interstitial Lung Disease (must meet all):
6. Diagnosis of SSc-ILD;
   2. Prescribed by or in consultation with a pulmonologist or rheumatologist;
   3. Age ≥ 18 years;
   4. Member meets (a and b): a. Pulmonary fibrosis affecting ≥ 10% of lung volume on HRCT; b. Additional signs of SSc are identified (see Appendix E);
7. Failure of a ≥ 3 consecutive month trial of cyclophosphamide or mycophenolate mofetil at up to maximally indicated doses, unless clinically significant adverse effects are experienced or both are contraindicated;

8. Baseline FVC ≥ 40% of predicted;

   7. Baseline DLCO ≥ 30% of predicted;
   8. Ofev is not prescribed concurrently with Esbriet;
   9. Member is not an active smoker as evidenced by recent (within the last 30 days) negative nicotine metabolite (i.e., cotinine) test;
   10. Dose does not exceed 300 mg (2 capsules) per day.
       Approval duration: 6 months Page 2 of 8

   CLINICAL POLICY Nintedanib D. Other diagnoses/indications (must meet 1 or 2):

9. 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) 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, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) 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, and CP.PMN.16 for Medicaid; or
10. 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, and CP.PMN.53 for Medicaid.
    II. Continued Therapy A. All Indications in Section I (must meet all):
11. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Member is responding positively to therapy;
    3. Ofev is not prescribed concurrently with Esbriet;
    4. If request is for a dose increase, new dose does not exceed 300 mg (2 capsules) per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
12. 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) 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, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) 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, and CP.PMN.16 for Medicaid; or

13. 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 Page 3 of 8

    CLINICAL POLICY Nintedanib 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, 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, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ACR: American College of Rheumatology ATS: American Thoractic Society CTD: connective tissue disease DLCO: carbon monoxide diffusing capacity FDA: Food and Drug Administration FVC: forced vital capacity IPF: idiopathic pulmonary fibrosis ILD: interstitial lung disease NCCN: National Comprehensive Cancer Network NSCLC: non-small cell lung cancer SSc-ILD: systemic sclerosis associated interstitial lung disease UIP: usual interstitial pneumonia 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 cyclophosphamide (Cytoxan®, Neosar®) mycophenolate mofetil (CellCept®) 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 SSc-ILD PO: 1 – 2 mg/kg/day IV: 600 mg/m2/month SSc-ILD*
    PO: 1 – 3 g/day 3 g/day Dose Limit/ Maximum Dose PO: 2 mg/kg/day IV: 600 mg/m2/month Appendix C: Contraindications/Boxed Warnings None reported Appendix D: American Thoracic Society (ATS) 2018 IPF Guidelines • ATS diagnostic criteria for IPF are built around pulmonary fibrosis findings on HRCT and exclusion of known causes of ILD (e.g., domestic and occupational environmental exposures, CTD, drug toxicity). • UIP is the hallmark radiologic pattern of IPF. Honeycombing is a distinguishing feature of UIP and must be present for a definite HRCT diagnosis of UIP to be made.
    Page 4 of 8

    CLINICAL POLICY Nintedanib • In patients with a probable or indeterminate UIP pattern, surgical lung biopsy or cellular analysis of bronchoalveolar lavage fluid is recommended to confirm the diagnosis of IPF. Appendix E: American College of Rheumatology (ACR) 2013 SSc Classification Criteria While the majority of patients with SSc experience skin thickening and variable involvement of internal organs, there is no one confirmatory test for SSc. Similar to the IPF guidelines above, ACR lists HRCT as a diagnostic method for determining pulmonary fibrosis in SSc- ILD. The other diagnostic parameters below are drawn from ACR’s scoring system purposed for clinical trials. While informative, ACR cautions that the scoring system parameters are not all inclusive of the myriad of SSc manifestations that may occur across musculoskeletal, cardiovascular, renal, neuromuscular and genitourinary systems.
    Examples of SSc skin/internal organ manifestations and associated laboratory tests: • Skin thickening of the fingers
    • Fingertip lesions
    • Telangiectasia
    • Abnormal nailfold capillaries
    • Raynaud’s phenomenon • SSc-ILD • Pulmonary arterial hypertension • SSc-related autoantibodies
    o Anticentromere o Anti–topoisomerase I [anti–Scl-70] o Anti–RNA polymerase III Appendix F: General Information • Smoking was associated with decreased exposure to Ofev, which may alter the efficacy profile of Ofev.
    • The Ofev pivotal studies included only patients with mild to moderate lung impairment per FVC and DLCO.
    V. Dosage and Administration
    Indication IPF, SSc-ILD, chronic fibrosing ILD with a progressive phenotype Dosing Regimen 150 mg PO BID approximately 12 hours apart (100 mg BID for patients with mild hepatic impairment or management of adverse reactions) Maximum Dose 300 mg/day VI. Product Availability
    Capsules: 100 mg, 150 mg VII.