CurrentColorado Rocky Mountain Health PlansPolicy 2026D0102K

Oxlumo (Lumasiran) and Rivfloza (Nedosiran) — Medical Benefit Drug Policy

Medical policy governing coverage and medical necessity criteria for lumasiran (Oxlumo) and nedosiran (Rivfloza) for treatment of primary hyperoxaluria type 1 (PH1) for UnitedHealthcare Commercial and Individual Exchange plans.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyOxlumo (Lumasiran) and Rivfloza (Nedosiran) — Medical Benefit Drug Policy

Policy CodePolicy 2026D0102K

Change TypeTemplate update

Effective DateJun 1, 2026

Next Review Date

Key ActionObtain prior authorization for initiation and reauthorization; approvals limited to no more than 12 months.

SourceLink

POLICY UPDATE CHANGES

Summary of Changes: Template update (06/01/2026).

12 monthsmax approval period

≥30eGFR threshold

Metabolic + geneticdiagnosis requirement

J0224, C9399, J3490codes referenced

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Coverage and Medical Necessity Criteria

Oxlumo (lumasiran) Initial Therapy

Covered when ALL of the following are met:

Oxlumo initial therapy criteria: Diagnosis of primary hyperoxaluria type 1 (PH1); patient is not receiving Oxlumo (lumasiran) in combination with Rivfloza (nedosiran); dosing is in accordance with the United States Food and Drug Administration approved labeling; diagnosis confirmed by metabolic testing (increased urinary oxalate excretion or increased plasma oxalate/glyoxylate) AND genetic testing confirming a mutation in the alanine:glyoxylate aminotransferase (AGT/AGXT) gene; prescribed by, or in consultation with, a specialist with expertise in PH1 (e.g., geneticist, nephrologist, urologist); patient has not received a liver transplant; initial authorization will be for no more than 12 months.See FDA labeling for age- and weight-based dosing

Specialist examples: geneticist, nephrologist, urologist.

Oxlumo (lumasiran) Continuation Therapy

Covered when ALL of the following are met:

Oxlumo continuation criteria: Submission of medical records documenting a positive clinical response to Oxlumo from pre-treatment baseline (e.g., decreased urinary oxalate concentrations, decreased urinary oxalate:creatinine ratio, decreased plasma oxalate concentrations); patient is not receiving Oxlumo in combination with Rivfloza (nedosiran); dosing is in accordance with the United States Food and Drug Administration approved labeling; prescribed by, or in consultation with, a specialist with expertise in PH1 (e.g., geneticist, nephrologist, urologist); patient has not received a liver transplant; reauthorization will be for no more than 12 months.Clinical response documented in medical records

Provide chart notes and laboratory values to support response.

Rivfloza (nedosiran) Initial Therapy

Covered when ALL of the following are met:

Rivfloza initial therapy criteria: Diagnosis of primary hyperoxaluria type 1 (PH1); patient is at least 2 years of age; patient has relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2); patient is not receiving Rivfloza (nedosiran) in combination with Oxlumo (lumasiran); dosing is in accordance with the United States Food and Drug Administration approved labeling; diagnosis confirmed by metabolic testing (increased urinary oxalate excretion or increased plasma oxalate/glyoxylate) AND genetic testing confirming a mutation in the alanine:glyoxylate aminotransferase (AGT/AGXT) gene; prescribed by, or in consultation with, a specialist with expertise in PH1 (e.g., geneticist, nephrologist, urologist); patient has not received a liver transplant; initial authorization will be for no more than 12 months.Age ≥ 2 years; eGFR ≥ 30 mL/min/1.73 m2

Specialist examples: geneticist, nephrologist, urologist.

Rivfloza (nedosiran) Continuation Therapy

Covered when ALL of the following are met:

Rivfloza continuation criteria: Submission of medical records documenting a positive clinical response to Rivfloza from pre-treatment baseline (e.g., decreased urinary oxalate concentrations, decreased urinary oxalate:creatinine ratio, decreased plasma oxalate concentrations); patient has relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2); patient is not receiving Rivfloza in combination with Oxlumo (lumasiran); dosing is in accordance with the United States Food and Drug Administration approved labeling; prescribed by, or in consultation with, a specialist with expertise in PH1 (e.g., geneticist, nephrologist, urologist); patient has not received a liver transplant; reauthorization will be for no more than 12 months.Clinical response documented and eGFR maintained ≥ 30 mL/min/1.73 m2

Provide chart notes and laboratory values to support response and maintained kidney function.

FDA Indications

FDA-indicated uses (informational only):

Lumasiran indication: Lumasiran (Oxlumo) is indicated for treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients.

FDA approval is informational; not by itself a basis for coverage.

Nedosiran indication: Rivfloza (nedosiran) is indicated to lower urinary oxalate levels in children 2 years of age and older and adults with primary hyperoxaluria type 1 (PH1) with relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2).eGFR ≥ 30 mL/min/1.73 m2

Efficacy demonstrated in clinical trials with urinary oxalate reductions; informational only.

Concurrent administration of Oxlumo (lumasiran) and Rivfloza (nedosiran) is excluded. The policy requires that patients receiving either agent must not be treated with the other simultaneously; coverage criteria and both initial and continuation authorization statements explicitly state the patient is "not receiving" the alternate siRNA product. Reviewers should identify combination therapy on prior authorization requests and medical records and deny or not authorize overlapping treatment courses in accordance with this policy.

Patients who have received a liver transplant are excluded from eligibility under the stated medical necessity criteria for both Oxlumo (lumasiran) and Rivfloza (nedosiran). The policy language for initial and continuation therapy explicitly requires that the patient "has not received a liver transplant," and this condition must be confirmed in the documentation submitted for authorization.

Use of these agents is limited to patients meeting the PH1 indication and the population characteristics described in the policy. The document specifies FDA-indicated uses and the coverage criteria require diagnosis confirmation for PH1; use for other forms of hyperoxaluria or non-PH1 diagnoses, or use inconsistent with the FDA-indicated populations (for example, nedosiran in patients with inadequate kidney function), is not supported by the stated criteria.

Rivfloza (nedosiran) is supported by the policy only for patients who are ≥ 2 years of age and have relatively preserved kidney function. The coverage language and FDA information cite a kidney function threshold of eGFR ≥ 30 mL/min/1.73 m2 and an age requirement of ≥ 2 years; requests for nedosiran in patients younger than 2 years or without the specified eGFR should not meet the stated criteria.

The excerpted policy includes statements of coverage criteria and exclusions but does not contain an explicit separate section labelling any uses as "not medically necessary." The document does, however, identify situations not supported by the criteria (for example, nedosiran use in patients with eGFR < 30 mL/min/1.73 m2 or age < 2 years) which would not meet the policy requirements.

Billing, Diagnosis, and Clinical Thresholds

Procedure/Billing codesHCPCS

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

Diagnosis codes (ICD-10)ICD-10

E72.530	Primary hyperoxaluria, type 1.
E72.538	Other specified primary hyperoxaluria.
E72.539	Primary hyperoxaluria, unspecified.
E72.540	Dietary hyperoxaluria.
E72.541	Enteric hyperoxaluria.
E72.548	Other secondary hyperoxaluria.
E72.549	Secondary hyperoxaluria, unspecified.

inv-13: eGFR — key clinical threshold (≥ 30 mL/min/1.73 m2) used for nedosiran and cited in trials

eGFR threshold for nedosiran≥ 30 mL/min/1.73 m2 (required for rivfloza initial and continuation eligibility)

eGFR cited in lumasiran trialeGFR ≥ 30 mL/min/1.73 m2 (ILLUMINATE‑A included patients ≥6 years with eGFR ≥ 30 mL/min/1.73 m2)

Clinical relevanceThreshold denotes ‘relatively preserved kidney function’ required for nedosiran and referenced in FDA indication text

inv-14: Urinary oxalate threshold — example numeric threshold and oxalate:creatinine reference

Urinary oxalate numeric example> 1 mmol/1.73 m2 per day (90 mg/1.73 m2 per day) — example threshold used in metabolic testing

Urinary oxalate:creatinine

Authorization, Documentation, and Reviewer Guidance

Prior Authorization

Prior Authorization Required

Prior Authorization is required for these medications. Initial authorizations will be for no more than 12 months; reauthorizations (continuation therapy) will also be for no more than 12 months. Reviewers should confirm dosing is in accordance with FDA‑approved labeling.

Initial and reauthorization duration: up to 12 months
Dosing must follow FDA labeling

Note

Policy Applicability and Authorization Guidance

This is a Medical Benefit Drug Policy intended to assist in interpreting UnitedHealthcare standard benefit plans; reviewers must check the member-specific benefit plan document and applicable federal or state mandates to determine plan applicability. Where member plan terms or applicable mandates conflict with this policy, the member-specific plan or mandate governs.

Applies to UnitedHealthcare Commercial and Individual Exchange benefit plans per template update — confirm member plan applicability

Clinical Background and Scope

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by pathogenic variants in the AGXT/AGT gene that result in overproduction of oxalate. Excess hepatic oxalate production leads to elevated urinary and plasma oxalate, with renal deposition of calcium oxalate crystals that can cause nephrolithiasis, nephrocalcinosis and progression to chronic kidney disease and end-stage renal disease. Lumasiran (Oxlumo) is an HAO1-directed small interfering RNA that reduces glycolate oxidase activity to lower urinary and plasma oxalate; nedosiran (Rivfloza) is an LDHA-directed small interfering RNA developed to lower urinary oxalate in patients with PH1. While these siRNA therapies target hepatic oxalate production, liver transplantation remains the only curative option for PH1.

Key Terms and Drug Descriptors

inv-26: Primary hyperoxaluria type 1 (PH1) — definition/key features

DefinitionPrimary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of glyoxylate metabolism caused by mutations in the AGXT/AGT gene leading to excessive oxalate production and calcium oxalate deposition, primarily affecting the kidneys, which can progress to end‑stage renal disease (ESRD).

PathophysiologyMutations in alanine:glyoxylate aminotransferase (AGT) impair glyoxylate metabolism, increasing oxalate production

Definitive treatmentLiver transplantation corrects the enzymatic defect and is the only curative intervention for PH1

inv-27: Lumasiran (Oxlumo) — key mechanism/indication descriptor

Mechanism of actionHAO1‑directed small interfering RNA (siRNA) that reduces glycolate oxidase (GO) levels in hepatocytes via RNA interference, lowering glyoxylate available for oxalate production.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyOxlumo (Lumasiran) and Rivfloza (Nedosiran) — Medical Benefit Drug Policy

Policy CodePolicy 2026D0102K

Change TypeTemplate update

Effective DateJun 1, 2026

Next Review Date

Key ActionObtain prior authorization for initiation and reauthorization; approvals limited to no more than 12 months.

SourceLink

On This Page

Increased urinary oxalate:creatinine ratio relative to normative values for age (used as an alternative metabolic test)

Use in diagnosis confirmationEither increased 24‑hour urinary oxalate or elevated spot oxalate:creatinine ratio may be used to confirm PH1 diagnosis prior to therapy

inv-15: eGFR threshold (repeat) — numeric threshold reference

Repeated eGFR threshold≥ 30 mL/min/1.73 m2 — stated as the eGFR threshold for relatively preserved kidney function (nedosiran indication)

Policy usageReferenced for both initial and continuation rivfloza eligibility (must be maintained for reauthorization)

Trial citationAlso cited in lumasiran ILLUMINATE‑A enrollment criteria (patients with eGFR ≥ 30 mL/min/1.73 m2)

Reference the member-specific benefit plan document for final coverage determination

Denial Risk

No Combination Therapy

Oxlumo (lumasiran) and Rivfloza (nedosiran) must not be used concurrently. Requests that indicate combination therapy will be denied.

Concurrent use of Oxlumo + Rivfloza is not allowed and is a denial criterion

Denial Risk

Potential Basis for Denial

Coverage decisions may be denied if the request is outside the indicated populations (for example, Rivfloza requires age ≥ 2 years and relatively preserved kidney function eGFR ≥ 30 mL/min/1.73 m2) or if required clinical parameters (e.g., age, eGFR) are out of range. FDA approval alone is not a basis for coverage.

Rivfloza initial criteria include age ≥ 2 years and eGFR ≥ 30 mL/min/1.73 m2
Oxlumo indicated for PH1 per FDA but plan criteria and documentation requirements apply
FDA approval is informational, not determinative for coverage

Documentation Required

Diagnosis Confirmation and Specialist Involvement

Diagnosis of PH1 must be confirmed and management should involve or be in consultation with a specialist (e.g., geneticist, nephrologist, urologist). Confirmation requires metabolic testing (e.g., elevated urinary oxalate or plasma oxalate/glyoxylate) and genetic testing demonstrating a pathogenic AGXT mutation. Patients who have received a liver transplant are excluded.

Diagnosis confirmation: metabolic testing and genetic testing confirming AGXT mutation
Specialist involvement: prescribed by or in consultation with a geneticist, nephrologist, or urologist
Excluded: prior liver transplant

Documentation Required

Required Documentation

Submit medical records to support the request: baseline and follow-up laboratory results (e.g., urinary oxalate concentrations, urinary oxalate:creatinine ratio, plasma oxalate), chart notes, and documentation of positive clinical response for continuation requests. Document dosing, prescribing specialist, and absence of concurrent therapy with the alternative agent.

Required documentation: pre-treatment baseline labs and follow-up labs showing clinical response
Include chart notes, dosing information, and specialist consultation documentation
Confirm absence of concurrent Oxlumo/Rivfloza therapy

Note

Benefit-Plan Dependent Considerations

Benefit-plan dependent considerations: applicability and coverage may vary by member plan. Some Certificates of Coverage may allow otherwise experimental/investigational treatments under specific conditions; state mandates may require coverage for certain off-label uses. Always reference the member-specific plan and document the clinical rationale when approval is granted despite plan limitations.

Consult the member-specific benefit plan document and any applicable state/federal mandates
If approving contrary to standard plan language, document the specific rationale tied to the member plan and clinical evidence

Indicated to lower urinary and plasma oxalate levels in pediatric and adult patients with primary hyperoxaluria type 1 (PH1).

Clinical trial referenceILLUMINATE trials evaluated urinary oxalate reductions (e.g., ILLUMINATE‑A required eGFR ≥ 30 mL/min/1.73 m2)

inv-28: Nedosiran (Rivfloza) — key mechanism/indication descriptor (age >=2 yrs note)

Mechanism of actionLDHA‑directed small interfering RNA (siRNA) that degrades LDHA mRNA in hepatocytes to reduce hepatic lactate dehydrogenase (LDH) and decrease oxalate production.

Indication and ageIndicated to lower urinary oxalate levels in children ≥ 2 years of age and adults with primary hyperoxaluria type 1 (PH1) with relatively preserved kidney function.

Kidney function requirementClinical criteria specify relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2) for nedosiran eligibility and continuation.

inv-29: Lumasiran (Oxlumo) — duplicate descriptor entry (include if inventory lists separately)

Mechanism summaryHAO1‑directed siRNA reducing glycolate oxidase to lower urinary and plasma oxalate in PH1 patients.

PopulationPediatric and adult patients with primary hyperoxaluria type 1 (PH1).

Clinical evidenceSupported by ILLUMINATE trials demonstrating significant reductions in urinary oxalate (e.g., ILLUMINATE‑A).

inv-30: Nedosiran (Rivfloza) — duplicate descriptor entry (include if inventory lists separately)

Mechanism summaryLDHA‑directed siRNA reducing hepatic LDH to decrease oxalate production.

Age and kidney functionIndicated in children ≥ 2 years and adults with PH1 and relatively preserved kidney function (e.g., eGFR ≥ 30 mL/min/1.73 m2).

Coverage notesPolicy requires age ≥2 years and eGFR threshold for initial and continuation approvals; concurrent use with lumasiran is excluded.