ModifiedmhnPolicy CP.PHAR.553

Belzutifan (Welireg) coverage

Defines medical necessity criteria, dosing, and authorization rules for belzutifan (Welireg) for VHL disease, renal cell carcinoma (clear cell), and pheochromocytoma/paraganglioma; applies to Centene-affiliated health plans and affected providers.

Policy Summary

Payermhn

PolicyBelzutifan (Welireg) coverage

Policy CodePolicy CP.PHAR.553

Change TypeAdded PPGL indicationrevised RCC criteriastandardized 12-month approvals

Effective DateDec 1, 2021

Next Review Date

Key ActionSubmit prior authorization with documentation (chart notes, labs, or other clinical information) showing the member meets indication-specific approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added new FDA-approved indication of pheochromocytoma or paraganglioma (PPGL).

For RCC, criteria revised to specify clear cell histology and allow bypass of prior PD-1/PD-L1 therapy per NCCN.

Continued approval duration revised to 12 months for all indications.

3Covered indications

120 mgMax daily dose

40 mgTablet strength

12 moApproval duration

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CentenePolicy ownership

Coverage Criteria

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the Health Plan's off‑label use policies (for example, CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or per the member's evidence of coverage documents.

Coverage determinations under this clinical policy are subject to the terms, conditions, exclusions, and limitations of the member's coverage documents (for example, evidence of coverage, certificate of coverage, or contract of insurance). The clinical policy itself does not guarantee payment; plan-level administrative policies, state and federal requirements, and the member's benefit design govern final coverage and claims administration.

Uses that are non‑FDA approved and that do not have adequate supporting evidence per the referenced off‑label use policies are considered not medically necessary and are not covered.

This clinical policy is a guide to medical necessity and is not medical advice. It does not prescribe treatment and is not intended to dictate how providers should care for members. Providers must exercise independent clinical judgment and remain solely responsible for medical advice and treatment decisions for their patients.

Initial Therapy

Initial therapy — authorization criteria differ by indication (VHL, RCC, PPGL)

Initial authorization criteria differ by indication; see the indication-specific criteria below and meet ALL listed for the requested diagnosis.

See individual indications: Refer to the indication-specific initial therapy criteria: VHL disease, renal cell carcinoma (clear cell), and PPGL. Authorization requires meeting all criteria listed for the chosen indication.

Continuation Therapy

Coding and Dosing

Diagnosis codes (not specified)ICD-10

ICD-10 unspecified in document

No explicit ICD-10 codes provided in this partial document

inv-10: Maximum daily dose — 120 mg

Maximum daily dose (adult)120 mg per day (3 x 40 mg tablets)

Corresponding tablet count3 tablets of 40 mg each

Applies toVHL disease and RCC; adults and pediatric ≥40 kg for PPGL

inv-11: Minimum daily dose for adults — 40 mg

Minimum adult daily dose40 mg once daily (1 x 40 mg tablet)

Dose floor languageDose is at least 40 mg (1 tablet) once daily for applicable indications

Pediatric note

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must meet the initial approval criteria and be prescribed by or in consultation with a specialist (oncologist) as specified in the clinical criteria. Provider must submit documentation (office notes, lab results, imaging, pathology, prior therapy records) supporting that the member meets all approval criteria.

Prior authorization required for Welireg (belzutifan) under this policy
Prescriber: oncology specialist or consult documented
Supportive documentation: chart notes, labs, pathology, prior treatment history

Documentation Required

Providers must submit supporting clinical documentation with the prior authorization request. Missing or insufficient documentation (including lack of evidence of prior required therapies or absence of specialist consultation) is a common reason for denial.

Step Therapy Requirements

Requirement	Details
Prior PD-1/PD-L1 inhibitor exposure
Member has previously received a PD-1 or PD-L1 inhibitor unless the provider documents the member previously received a first‑line regimen containing only a VEGF‑TKI (NCCN exception)

Quantity Limits

inv-27: Belzutifan (Welireg) — quantity limit entry (group 1)

DrugBelzutifan (Welireg)

Quantity limit (group 1)3 tablets per day (3 x 40 mg) — corresponds to 120 mg/day maximum

Tablet strength40 mg tablet

inv-28: Belzutifan (Welireg) — quantity limit entry (group 2)

DrugBelzutifan (Welireg)

Quantity limit (group 2)2 tablets per day (2 x 40 mg) — corresponds to 80 mg/day maximum for pediatric patients <40 kg

Tablet strength

Definitions

inv-21: VHL definition — VHL: von Hippel-Lindau disease

AbbreviationVHL

Definitionvon Hippel-Lindau disease

ContextUsed in policy to denote VHL disease associated tumors (RCC, CNS hemangioblastomas, pNET)

inv-22: PPGL definition — PPGL: pheochromocytoma or paraganglioma

AbbreviationPPGL

Definitionpheochromocytoma or paraganglioma

UsageIndication included in policy for patients ≥12 years with locally advanced, unresectable, or metastatic disease

Background

Belzutifan (Welireg) is a hypoxia‑inducible factor‑2 alpha (HIF‑2α) inhibitor approved to treat specific tumor types associated with von Hippel‑Lindau (VHL) disease, advanced renal cell carcinoma (clear cell) after prior systemic therapy, and locally advanced/metastatic pheochromocytoma or paraganglioma (PPGL) in eligible patients. Dosing guidance in the policy aligns with the product labeling and formulary dosing limits: tablet strength is 40 mg and the adult maximum daily dose is 120 mg. This clinical policy references FDA prescribing information and relevant guidance (for example, NCCN) when defining approved indications, age/weight‑based dosing limits, and duration of authorization.

Site of Care

Note

Site of care — no restrictions specified

No site‑of‑care restrictions are specified in this section of the policy.

Setting indicated in policy: home — no restrictions noted for site of care.

Policy Summary

Payermhn

PolicyBelzutifan (Welireg) coverage

Policy CodePolicy CP.PHAR.553

Change TypeAdded PPGL indicationrevised RCC criteriastandardized 12-month approvals

Effective DateDec 1, 2021

Next Review Date

Key ActionSubmit prior authorization with documentation (chart notes, labs, or other clinical information) showing the member meets indication-specific approval criteria.

SourceLink

On This Page

Pediatric patients <40 kg have different maxima (see policy) but adult minimum remains 40 mg

Examples: prior PD-1/PD-L1 and VEGF-TKI therapy records for RCC; documentation of VHL diagnosis and indications for therapy; evidence when using off-label dosing or regimens

If requesting an off-label dose/regimen, include supporting peer-reviewed literature or guideline references

Step Therapy

Step Therapy Governed by Plan Rules

Step therapy and therapeutic sequencing are governed by the member's benefit plan rules and the Health Plan's administrative procedures. For RCC, approval requires prior receipt of both a PD-1/PD-L1 inhibitor and a VEGF-TKI unless the provider documents prior use of a first-line regimen containing only a VEGF-TKI or other plan-allowed exceptions (e.g., NCCN-recommended exceptions). Providers should consult the member's plan for any additional step-therapy requirements and for guidance on allowable sequencing or exceptions.

RCC-specific step therapy: prior PD-1/PD-L1 and VEGF-TKI required unless documented exception
Plan-level rules and exceptions (e.g., NCCN recommendations) apply and may vary by contract

Note

Coverage and Submission Expectations

Coverage is subject to the member's benefit documents and the Health Plan's administrative policies and procedures. The Health Plan determines final coverage and prior authorization processes; providers should follow the Health Plan's submission requirements and timelines.

Coverage decisions subject to evidence of coverage, benefit contract terms, and applicable state/federal regulations
Follow Health Plan-specific prior authorization submission portals and instructions

Denial Risk

Denials may be issued for non‑FDA indications that lack sufficient supporting evidence, for missing required documentation, or for failure to meet step-therapy requirements. If denied, providers may submit additional supporting information or pursue appeals per the Health Plan's policies.

Common denial triggers: missing specialist consult, absent prior therapy documentation, non‑approved indication without supporting literature
Appeal and resubmission instructions: follow plan-level administrative policies

inv-23: Health Plan definition — defines 'Health Plan' as plan adopted and operated/ administered by Centene affiliates

TermHealth Plan

DefinitionA health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC or any of its affiliates

ImplicationCoverage decisions and administrative procedures are subject to the Health Plan's terms, conditions, exclusions, limitations, and applicable law