ModifiedCentenePolicy CP.PHAR.619

Nedosiran (Rivfloza) — Coverage Criteria for Primary Hyperoxaluria Type 1

Defines medical necessity and prior authorization criteria for Rivfloza (nedosiran) for treatment of primary hyperoxaluria type 1 (PH1) for Centene-affiliated health plans across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyNedosiran (Rivfloza) — Coverage Criteria for PH1

Policy CodePolicy CP.PHAR.619

Change TypeMaterial revisions (age/dosing, prescriber list, approval duration, concomitant use exclusion)

Effective DateSep 29, 2023

Next Review Date

Key ActionSubmit prior authorization with documentation of PH1 confirmation, age ≥2, eGFR ≥30, elevated UOx or age‑adjusted UOx:Cr, prior pyridoxine trial, weight, and prescriber specialty.

SourceLink

POLICY UPDATE CHANGES

Added medical geneticist to initial prescriber list.

Expanded pediatric age indication to include children ≥ 2 years and updated dosing and prefilled syringe requirement.

Extended initial approval duration to 12 months for maintenance medication.

Added exclusion for concomitant use of Rivfloza with Oxlumo.

Age ≥ 2 yearsminimum age for FDA indication and policy coverage

eGFR ≥ 30required minimum kidney function for indication

UOx > 0.70 mmol/1.73 m2/24 hbiomarker threshold to qualify

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Dose limitsmonthly dosing by weight/age strata

12 mo / 6 motypical authorization length

Coverage Criteria for Nedosiran (Rivfloza)

Initial Therapy — PH1

Covered when ALL of the following are met:

PH1 confirmation: Diagnosis of PH1 confirmed by genetic testing showing AGXT mutations OR liver biopsy confirming AGT enzyme deficiency

Prescriber specialty: Prescribed by or in consultation with an endocrinologist, hepatologist, nephrologist, urologist, or medical geneticist

Age: Patient is ≥ 2 years of age

Kidney function: Documentation of estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2

Oxalate evidence: Either UOx excretion > 0.70 mmol/1.73 m2/24 h confirmed on repeat testing OR spot UOx:Cr molar ratio greater than normal for age (see Appendix D) confirmed on repeat testing

See Appendix D for age-specific ranges

Pyridoxine trial: Failure to achieve normalization of UOx after at least 3 months of pyridoxine (vitamin B6) at up to maximally indicated doses, unless contraindicated or intolerant

No liver transplant: Member has not had a liver transplant

No concomitant Oxlumo: Rivfloza is not prescribed concurrently with Oxlumo

Weight documentation: Documentation of member's current body weight (kg)

Formulation and dose limits: Request must be for a prefilled syringe unless the monthly dose is < 128 mg; monthly dose must not exceed limits by age/weight: weight ≥ 50 kg = 160 mg/month (1 prefilled syringe); age ≥ 12 years and < 50 kg = 128 mg/month (1 prefilled syringe); age 2-11 years and < 50 kg: if < 39 kg = 3.3 mg/kg/month, if ≥ 39 kg = 128 mg/month (1 prefilled syringe)

See dosing table/product availability

Continuation Therapy — PH1

Covered for continuation when ALL of the following are met:

Previous approval or continuity: Member currently receiving medication via Centene benefit and previously met initial approval criteria OR member currently receiving medication and enrolled in a state/product with continuity of care regulations

Response to therapy: Either decrease from baseline in UOx excretion of > 30% OR improvement in PH1 symptoms (e.g., nephrolithiasis, nephrocalcinosis, kidney function, ischemic skin ulcers, metabolic bone disease, refractory anemia, cardiomyopathy, conduction abnormalities) accompanied by a decrease in UOx excretion or improvement in spot UOx:Cr

One of the listed response criteria must be met

No liver transplant: Member has not had a liver transplant

No concomitant Oxlumo: Rivfloza is not prescribed concurrently with Oxlumo

Non‑FDA approved indications not specifically addressed by this clinical policy are excluded from coverage unless the request is supported by sufficient documentation of efficacy and safety in accordance with the applicable 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 by the member's evidence of coverage documents. Requests for off‑label use should reference and meet the requirements of those off‑label policies to be considered for approval.

All coverage determinations under this clinical policy are made in the context of the member’s specific benefit plan and are subject to the terms, conditions, exclusions, and limitations of the applicable coverage documents (for example, evidence of coverage, certificate of coverage, policy, or contract of insurance). This policy is a guide to medical necessity and to assist in making coverage decisions; it does not constitute a guarantee of payment and does not override any contractual or regulatory requirements that apply to the member’s plan.

Use of Rivfloza (nedosiran) for indications that are not FDA‑approved and that are not specifically addressed in this policy will be considered not authorized unless the provider supplies sufficient evidence of safety and efficacy according to the referenced off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or the member’s evidence of coverage. Providers requesting coverage for off‑label indications must follow those off‑label policies and provide the documentation they require.

Coding and Laboratory Thresholds

HCPCS codes referencedHCPCS

C9399	Unclassified drugs or biologicals.
J3490	Unclassified drugs.

inv-07: UOx excretion / UOx:Cr — lab thresholds: UOx > 0.70 mmol/1.73 m2/24 h OR spot UOx:Cr greater than age-normal range (see Appendix D).

Urinary oxalate (24‑hr)UOx excretion > 0.70 mmol/1.73 m2/24 h (confirmed on repeat testing)

Spot UOx:CrSpot urinary oxalate-to-creatinine (UOx:Cr) molar ratio greater than normal for age (see Appendix D), confirmed on repeat testing

Reference for age rangesSee Appendix D for age-specific spot UOx:Cr reference ranges and normal values

Normal UOx definitionNormal UOx excretion defined as < 0.50 mmol (<45 mg)/1.73 m2/day

inv-08: eGFR threshold — eGFR ≥ 30 mL/min/1.73 m2 requirement for coverage.

eGFR requirementDocumented estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Rivfloza (nedosiran). Providers must submit documentation (such as office chart notes, laboratory results, genetic testing or liver biopsy reports, current body weight, and eGFR) supporting that the member meets all approval criteria. This documentation should demonstrate diagnosis confirmation, baseline and repeat urinary oxalate (UOx) or spot UOx:Cr results, prior pyridoxine (vitamin B6) trial details, and prescriber specialty involvement.

Prior authorization required
Submit office notes, labs, genetic test or liver biopsy confirming AGXT mutation or AGT deficiency
Document eGFR ≥ 30 mL/min/1.73 m2 and current body weight (kg)
Provide baseline and repeat UOx excretion (>0.70 mmol/1.73 m2/24 h) or age-adjusted spot UOx:Cr above normal (see Appendix D)
Document at least a 3-month trial of pyridoxine at maximally indicated doses with failure to normalize UOx, unless contraindicated or not tolerated
Prescriber must be an endocrinologist, hepatologist, nephrologist, urologist, or medical geneticist (or in consultation with one)
Dose and formulation requirements: prefilled syringe required unless monthly dose <128 mg; age/weight–based maximum dosing applies

Background and Clinical Context

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disorder characterized by deficient alanine:glyoxylate aminotransferase (AGT) activity, leading to overproduction of oxalate, elevated urinary oxalate (UOx), and progressive kidney injury including nephrolithiasis and nephrocalcinosis. Nedosiran (Rivfloza) is an LDHA‑directed small interfering RNA therapy indicated to lower urinary oxalate in patients with PH1 aged ≥ 2 years with relatively preserved renal function (typically eGFR ≥ 30 mL/min/1.73 m2). By targeting LDHA in the liver, nedosiran reduces hepatic oxalate production, which can decrease UOx excretion and may reduce the clinical consequences of systemic oxalosis and kidney damage in affected patients.

Definitions and Drug Summary

inv-19: Nedosiran (Rivfloza) — brief drug definition, indication, age and kidney function summary.

Drug class and trade nameNedosiran (Rivfloza) — an LDHA‑directed small interfering RNA (siRNA)

IndicationIndicated to lower urinary oxalate (UOx) levels in patients with primary hyperoxaluria type 1 (PH1)

Age indicationFDA‑approved for children aged ≥ 2 years and adults

Kidney function requirementApproved for patients with relatively preserved kidney function, e.g., eGFR ≥ 30 mL/min/1.73 m2

inv-20: Normal UOx excretion — numeric normal ranges and Appendix D reference.

Numeric normal (24‑hr)Normal UOx excretion: < 0.50 mmol (<45 mg)/1.73 m2/day

Revision History and Policy Changes

2024-11-15policy_revision

Added medical geneticist to the list of authorized prescriber specialties and added HCPCS codes C9399 and J3490.

2025-04-16policy_revision

Expanded pediatric age indication and dosing to include children aged ≥ 2 years and added requirement that requests be for a prefilled syringe unless monthly dose < 128 mg (RT4 pediatric extension).

2025-11-06policy_revision

Policy Summary

PayerCentene

PolicyNedosiran (Rivfloza) — Coverage Criteria for PH1

Policy CodePolicy CP.PHAR.619

Change TypeMaterial revisions (age/dosing, prescriber list, approval duration, concomitant use exclusion)

Effective DateSep 29, 2023

Next Review Date

Key ActionSubmit prior authorization with documentation of PH1 confirmation, age ≥2, eGFR ≥30, elevated UOx or age‑adjusted UOx:Cr, prior pyridoxine trial, weight, and prescriber specialty.

SourceLink

On This Page

Weight documentation: Documentation of current body weight (kg)

Formulation and dose limits (renewal): Request must be for a prefilled syringe unless the monthly dose is < 128 mg; if request is for a dose increase, new dose must not exceed age/weight maximums (weight ≥ 50 kg = 160 mg/month; age ≥ 12 & < 50 kg = 128 mg/month; age 2-11 & < 50 kg: < 39 kg = 3.3 mg/kg/month; ≥ 39 kg = 128 mg/month)

Purpose of thresholdReflects requirement for relatively preserved kidney function for use of nedosiran in PH1

DocumentationeGFR must be provided in supporting clinical documentation for approval

Note

Coverage Decision Caveat

Coverage decisions are guided by this clinical policy but are subject to the member’s specific coverage documents, state and federal requirements, and applicable Health Plan administrative policies and procedures. Meeting criteria does not guarantee payment.

Note

Provider Professional Judgment

Providers are expected to exercise professional medical judgment. This policy is not intended to dictate care; providers remain solely responsible for medical advice and treatment decisions.

Denial Risk

Non‑FDA Indications

Requests for non‑FDA approved (off‑label) indications will be denied unless sufficient documentation of efficacy and safety is provided in accordance with the applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Denial Risk

Concomitant Therapy Exclusion

Concurrent prescription of Rivfloza with Oxlumo is an exclusion and will result in non‑coverage/denial.

Documentation Required

Prior Authorization Guidance

Administrative note: This policy is intended to assist in coverage decisions and the prior authorization process. Providers should follow the Health Plan's prior authorization submission procedures and include all requested supporting clinical information to avoid processing delays.

Documentation Required

Required Clinical Documentation

Required clinical documentation to include with the PA request: diagnosis confirmation (genetic testing showing AGXT mutation or liver biopsy demonstrating AGT deficiency), office notes detailing clinical course, baseline and repeat UOx or spot UOx:Cr results (with reference to Appendix D age ranges), documentation of pyridoxine trial (duration, dose, response, or intolerance), current eGFR, current body weight, and documentation of prescriber specialty or consultation.

Spot UOx:Cr referenceAppendix D provides age-specific spot UOx:Cr molar ratio reference ranges (see Appendix D)

Selected age ranges (spot UOx:Cr)Examples from Appendix D: 2–5 years normal < 98–101 mmol/mol; 5–14 years < 70–82 mmol/mol; >16 years < 40 mmol/mol

inv-21: Health Plan — definition of 'Health Plan' as used in this policy.

Definition'Health Plan' means a 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 such health plan's affiliates, as applicable.

ScopeApplies to the Health Plan's use of this clinical policy for making coverage decisions and administering benefits

Non‑contractual natureThis clinical policy is a guide to medical necessity and does not constitute a contract or guarantee of payment

Extended initial approval duration for maintenance medication from 6 to 12 months effective in the 1Q 2026 annual review.

2024-02-29policy_revision

Added explicit exclusion prohibiting concomitant use of Rivfloza with Oxlumo across initial and continued therapy criteria.