Belzutifan (Welireg) Form

Belzutifan (Welireg®) is a hypoxia-inducible factor inhibitor. FDA Approved Indication(s) Welireg is indicated for the treatment of adult patients with: • von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery • Advanced RCC following a programmed death receptor-1 (PD-1) or programmed death- ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) 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 Welireg is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Von Hippel-Lindau Disease (must meet all):

1. Diagnosis of VHL disease requiring therapy for associated RCC, CNS hemangioblastomas, or pNET, but not requiring immediate surgery;
2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For Welireg requests, member must use belzutifan, if available, unless contraindicated or clinically significant adverse effects are experienced;

3. Welireg is prescribed as single-agent therapy;

   6. Request meets one of the following (a or b): a. Dose meets both of the following (i and ii): i. Dose does not exceed 120 mg (3 tablets) once daily;
      ii. Dose is at least 40 mg (1 tablet) once daily; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
      Approval duration: 6 months
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   CLINICAL POLICY Belzutifan B. Renal Cell Carcinoma (must meet all):

4. Diagnosis of advanced (unresectable, locally advanced, relapsed, or metastatic) RCC;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Member has previously received both of the following (a and b): a. PD-1 or PD-L1 inhibitor (see Appendix B for examples); b. VEGF-TKI (see Appendix B for examples);
5. For Welireg requests, member must use belzutifan, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. Welireg is prescribed as single-agent therapy;
   7. Request meets one of the following (a or b): a. Dose meets both of the following (i and ii): i. Dose does not exceed 120 mg (3 tablets) once daily;
      ii. Dose is at least 40 mg (1 tablet) once daily; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
      Approval duration: 6 months
      C. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Welireg for a covered indication and has received this medication for at least 30 days;
10. Member is responding positively to therapy;
    3. For Welireg requests, member must use belzutifan, if available, unless contraindicated or clinically significant adverse effects are experienced;

11. Welireg is prescribed as single-agent therapy; Page 2 of 6

    CLINICAL POLICY Belzutifan

12. If request is for a dose increase, request meets one of the following (a or b): a. New dose meets both of the following (i and ii): i. Dose does not exceed 120 mg (3 tablets) once daily; ii. Dose is at least 40 mg (1 tablet) once daily; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
13. 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

14. 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.
    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 CNS: central nervous system FDA: Food and Drug Administration PD-1: programmed death receptor-1
    PD-L1: programmed death ligan 1 pNET: pancreatic neuroendocrine tumors RCC: renal cell carcinoma
    TKI: tyrosine kinase inhibitor
    VEGF: vascular endothelial growth factor
    VHL: von Hippel-Lindau 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.
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    CLINICAL POLICY Belzutifan Drug Name Examples of PD-1 or PD-L1 inhibitors: avelumab, nivolumab, pembrolizumab Examples of VEGF-TKIs: axitinib, cabozantinib, lenvatinib, pazopanib, sorafenib, sunitinib, tivozanib 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. Varies Varies Dosing Regimen Varies Dose Limit/ Maximum Dose Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): embryo-fetal toxicity V. Dosage and Administration
    Indication VHL disease, RCC Dosing Regimen 120 mg PO QD Maximum Dose 120 mg/day VI. Product Availability
    Tablet: 40 mg VII.