ModifiedUnitedHealthcarePolicy 2025D0102I

Oxlumo (lumasiran) and Rivfloza (nedosiran)

UnitedHealthcare medical benefit drug policy governing coverage criteria, initial and continuation authorization, and applicable coding for Oxlumo (lumasiran) and Rivfloza (nedosiran) for treatment of primary hyperoxaluria type 1 (PH1). Applies to provider-administered and specialty pharmacy administration per FDA labeling and plan benefit rules.

Policy Summary

PayerUnitedHealthcare

PolicyOxlumo (lumasiran) and Rivfloza (nedosiran)

Policy CodePolicy 2025D0102I

Change TypeCoverage criteria revised (Rivfloza age lowered to ≥2 years)

Effective DateJul 1, 2025

Next Review Date

Key ActionFor initial therapy, submit metabolic testing and genetic testing confirming AGXT mutation and ensure diagnosis is by or in consultation with a PH1 specialist; initial authorizations will be for no more than 12 months.

POLICY UPDATE CHANGES

Revised coverage criteria for initial therapy for Rivfloza: replaced criterion requiring 'the patient is at least 9 years of age and older' with 'the patient is at least 2 years of age and older'.

2Drugs covered (Oxlumo, Rivfloza)

1Indication (PH1)

12 monthsMax initial authorization duration

eGFR ≥30Rivfloza kidney function requirement

Coverage Summary

UnitedHealthcare medical benefit drug policy for Oxlumo (lumasiran) and Rivfloza (nedosiran) covers treatment of primary hyperoxaluria type 1 (PH1) under specified criteria and applies to both provider‑administered and specialty pharmacy routes per FDA labeling and plan benefit rules. Coverage stance: covered_with_criteria. The policy addresses both initial and continuation authorizations (each limited to no more than 12 months) and requires specialist involvement. Rivfloza eligibility includes patients who are at least 2 years of age with relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2). Concurrent use of Oxlumo and Rivfloza is explicitly excluded.

Key thresholds and stats

Urinary oxalate excretion threshold> 1 mmol/1.73 m2 per day (90 mg/1.73 m2 per day)

eGFR threshold (Rivfloza)>= 30 mL/min/1.73 m2

Max initial authorization duration12 months

Drugs covered2 (Oxlumo, Rivfloza)

Oxlumo — Initial Therapy Criteria

Oxlumo — Proven / Medically Necessary

Covered when ALL of the following are met:

ALL of the following

Diagnosis of PH1
Diagnosis of PH1 by, or in consultation with, a specialist (e.g., geneticist, nephrologist, urologist) with expertise in the diagnosis of PH1
Diagnostic confirmation (BOTH required)
- Metabolic testing demonstrating one of the following: Increased urinary oxalate excretion (e.g., greater than 1 mmol/1.73 m2 per day [90 mg/1.73 m2 per day], increased urinary oxalate:creatinine ratio relative to normative values for age); or Increased plasma oxalate and glyoxylate concentrations
- Genetic testing has confirmed a mutation in the alanine:glyoxylate aminotransferase (AGT or AGXT) gene
Patient has not received a liver transplant
Patient is not receiving Oxlumo in combination with Rivfloza (nedosiran)
Dosing is in accordance with the United States Food and Drug Administration approved labeling
Initial authorization will be for no more than 12 months

Prior Authorization

Initial authorization time limit

Initial authorization for Oxlumo (lumasiran) or Rivfloza (nedosiran) will be for no more than 12 months.

Denial Risk

Concomitant therapy excluded — denial risk

Claims may be denied or not approved if the patient is receiving Oxlumo and Rivfloza in combination; concurrent use is explicitly excluded in the coverage criteria.

Oxlumo — Continuation of Therapy Criteria

Oxlumo — Continuation of Therapy

Reauthorization when ALL of the following are met:

ALL of the following

Documentation of positive clinical response to Oxlumo (e.g., decreased urinary oxalate concentrations, decreased urinary oxalate:creatinine ratio, decreased plasma oxalate concentrations) compared to pre-treatment baseline
Patient has not received a liver transplant
Patient is not receiving Oxlumo in combination with Rivfloza (nedosiran)
Prescribed by, or in consultation with, a specialist (e.g., geneticist, nephrologist, urologist) with expertise in the treatment of PH1
Dosing is in accordance with the United States Food and Drug Administration approved labeling
Reauthorization will be for no more than 12 months

Prior Authorization

Reauthorization time limit and response requirement

Reauthorization (continuation) approvals will be for no more than 12 months and require documentation of a positive clinical response for continuation.

Documentation Required

Required documentation for continuation response

For continuation, submit medical records (e.g., chart notes, laboratory values) demonstrating decreased urinary oxalate concentrations, decreased urinary oxalate:creatinine ratio, or decreased plasma oxalate concentrations compared to pre-treatment baseline.

Rivfloza — Initial Therapy Criteria (provider-administered)

Documentation Required

Diagnostic confirmation required (metabolic and genetic testing)

For initial therapy, submit metabolic testing (urinary oxalate excretion or plasma oxalate/glyoxylate) and genetic testing confirming an AGXT (AGT) mutation; the diagnosis must be made by, or in consultation with, a PH1 specialist.

Documentation Required

Specialist prescribing requirement

Drugs must be prescribed by, or in consultation with, a specialist (geneticist, nephrologist, or urologist) with expertise in PH1; include documentation of specialist involvement with the prescription.

Rivfloza — Continuation of Therapy (provider-administered)

Prior Authorization

Rivfloza reauthorization time limit and response requirement

Reauthorization for Rivfloza continuation will be for no more than 12 months and requires submission of documentation demonstrating a positive clinical response to therapy.

Exclusions and Not Covered Uses

Explicit exclusions and provider actions: patients who have received a liver transplant are not eligible for coverage. Concurrent use of Oxlumo and Rivfloza is prohibited and may result in claim denial. Uses outside the FDA‑approved dosing, age, or renal function labeling (for example, dosing not in accordance with the United States Food and Drug Administration approved labeling, or patients younger/older than labeled age limits or with eGFR below specified thresholds) are not covered. Dosing must follow the FDA‑approved labeling.

Provider Actions & Requirements

Prior Authorization

Initial authorization time limit

Initial authorization for Oxlumo (lumasiran) or Rivfloza (nedosiran) will be for no more than 12 months.

Prior Authorization

Reauthorization time limit and response requirement

Reauthorization (continuation) approvals will be for no more than 12 months and require documentation of a positive clinical response for continuation.

Documentation Required

Diagnostic confirmation required (metabolic and genetic testing)

For initial therapy, submit metabolic testing (urinary oxalate excretion or plasma oxalate/glyoxylate) and genetic testing confirming an AGXT (AGT) mutation; diagnosis must be by or in consultation with a PH1 specialist.

Documentation Required

Continuation response documentation

For continuation, submit medical records (chart notes, laboratory values) documenting decreased urinary oxalate concentrations, decreased urinary oxalate:creatinine ratio, or decreased plasma oxalate concentrations from pre-treatment baseline.

Denial Risk

Concomitant therapy excluded — denial risk

Concurrent use of Oxlumo and Rivfloza is explicitly excluded in the coverage criteria and may result in claim denial or non-approval.

Documentation Required

Specialist prescribing requirement (documentation)

Prescriptions must be by, or in consultation with, a PH1 specialist (e.g., geneticist, nephrologist, urologist); include specialist documentation with the medical records.

Clinical Evidence

-65%ILLUMINATE-A: LS mean -65% (lumasiran) vs -12% (placebo); between-group difference 53%, p<0.0001

71%ILLUMINATE-B: 71% reduction in pediatric spot urinary oxalate:creatinine ratio (lumasiran)

49%PHOX2: nedosiran −37% vs 12% placebo (between-group difference 49%)

Mechanism summary: both lumasiran and nedosiran are small interfering RNA (siRNA) therapies that reduce hepatic production of oxalate by targeting specific hepatocyte mRNAs—lumasiran (HAO1/GO) and nedosiran (LDHA/LDH)—thereby lowering hepatic oxalate generation in PH1.

Background & Definitions

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the AGXT gene (encoding alanine:glyoxylate aminotransferase) resulting in hepatic overproduction of oxalate and increased risk of kidney deposition and end‑stage renal disease (ESRD). Oxlumo (lumasiran) and Rivfloza (nedosiran) lower urinary and plasma oxalate by RNA interference‑mediated reduction of hepatic enzymes involved in oxalate production.

Definitions:

PH1: Primary hyperoxaluria type 1, an autosomal recessive enzymatic defect (AGXT/alanine:glyoxylate aminotransferase) causing excessive hepatic oxalate production and risk of kidney damage/ESRD.

eGFR: Estimated glomerular filtration rate, a measure of kidney function used in the policy to define relative preservation of renal function (e.g., eGFR ≥ 30 mL/min/1.73 m2 is required for Rivfloza eligibility).

Revision History

07/01/2025material_changeLatest

Revised coverage criteria for initial Rivfloza therapy: replaced the prior minimum age requirement of 9 years with a new minimum age of 2 years for treatment eligibility. Supporting sections updated (Benefit Considerations, FDA, References) and prior policy version 2024D0102H archived.

Policy Summary

PayerUnitedHealthcare

PolicyOxlumo (lumasiran) and Rivfloza (nedosiran)

Policy CodePolicy 2025D0102I

Change TypeCoverage criteria revised (Rivfloza age lowered to ≥2 years)

Effective DateJul 1, 2025

Next Review Date

On This Page

C9399	Unclassified drugs or biologicals
J0224	Injection, lumasiran, 0.5 mg
J3490	Unclassified drugs

OpenPayer

Oxlumo (lumasiran) and Rivfloza (nedosiran)

Coverage Summary

Oxlumo — Initial Therapy Criteria

Oxlumo — Continuation of Therapy Criteria

Rivfloza — Initial Therapy Criteria (provider-administered)

Rivfloza — Continuation of Therapy (provider-administered)

Exclusions and Not Covered Uses

Applicable Codes

Provider Actions & Requirements

Clinical Evidence

Background & Definitions

Revision History