ModifiedCentenePolicy CP.PHAR.457

Clinical Policy: Givosiran (Givlaari)

Defines medical necessity criteria, dosing limits, and authorization requirements for Givlaari (givosiran) for members with acute hepatic porphyria across Centene lines of business.

Policy Summary

PayerCentene

PolicyClinical Policy: Givosiran (Givlaari)

Policy CodePolicy CP.PHAR.457

Change TypeMaterial clinical and coverage revisions (diagnostic criteria, attack threshold, approval duration, concurrent therapy restriction).

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with confirmatory diagnostic evidence (genetic testing OR recent elevated urine ALA/PBG), documentation of attack history or prophylactic Panhematin use, and current body weight in kg.

SourceLink

POLICY UPDATE CHANGES

Revised confirmatory diagnostic criteria from requiring both genetic testing and ALA/PBG to either genetic testing or elevated ALA/PBG; clarified that ALA/PBG urine sample must be recent (within the past year).

Revised criterion regarding recurrent porphyria attacks from '≥ 2 attacks in 6-month period' to '4 attacks per year' per AGA guidelines.

Added criterion that Panhematin, as a prophylactic treatment, is not prescribed concurrently with Givlaari to continued therapy.

Extended initial approval duration from 6 to 12 months for this maintenance medication.

Added documentation requirement for member's current body weight (in kg).

Added requirement that a hepatologist may prescribe or be in consultation with for givosiran.

4/yrAttack threshold

≥18Minimum age

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12 moApproval duration (Medicaid/HIM)

Coverage Criteria for Givosiran (Givlaari)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial Approval - AHP: 1) Diagnosis of AHP confirmed by either: (a) subtype-specific genetic testing (e.g., HMBS for AIP; CPOX for HCP; PPOX for VP; ALAD for ALAD porphyria) OR (b) history of at least a four-fold increase in urinary ALA or PBG on a random urine sample within the past year; 2) Prescribed by or in consultation with a gastroenterologist, hematologist, hepatologist, or neurologist; 3) Age ≥ 18 years; 4) Either (a) member is currently receiving prophylactic Panhematin therapy (e.g., once or twice weekly on a regular basis) OR (b) member has experienced 4 or more porphyria attacks per year requiring hospitalization, urgent healthcare visit, or intravenous Panhematin; 5) Panhematin is not prescribed prophylactically concurrently with Givlaari (use of Panhematin for acute attacks while on Givlaari is allowed); 6) Documentation of member's current body weight in kilograms; 7) Requested dose does not exceed 2.5 mg/kg once monthly.dose <= 2.5 mg/kg monthly

Prior authorization may be required

inv-03: Initial Therapy / Coverage Criteria

Covered when ALL of the following are met (as revised):

Diagnostic confirmation: Confirmatory diagnostic criteria require either genetic testing consistent with acute hepatic porphyria OR elevated urinary ALA/PBG (with the urine sample collected within the past year)

Revised in 1Q 2022

Attack frequency: Member has recurrent porphyria attacks meeting threshold4 attacks/year

Revised in 1Q 2026

Prescriber specialty or consultation: Prescribed by or in consultation with a hepatologist (addition noted 1Q 2023)

Added 1Q 2023

Documentation includes member's current body weight in kilograms

Added 1Q 2024

inv-02: Continuation Therapy

Covered when ALL of the following are met:

Continuation - AHP: 1) Member currently receiving medication via Centene benefit or previously met initial criteria OR continuity of care applies; 2) Member is responding positively to therapy as evidenced by either (a) decreased number of porphyria attacks requiring hospitalization, urgent healthcare visit, or IV Panhematin administration OR (b) if member was receiving prophylactic Panhematin prior to Givlaari initiation, no increase in such attacks; 3) Panhematin is not prescribed prophylactically concurrently with Givlaari (use of Panhematin for acute attacks while on Givlaari is allowed); 4) Documentation of member's current body weight in kilograms; 5) Any requested dose increase does not exceed 2.5 mg/kg once monthly.

inv-04: Continued Therapy

Continued therapy covered when ALL of the following are met:

Ongoing clinical benefit: Member demonstrates ongoing reduction in attack frequency or other clinical benefit as determined by the prescriber

No concurrent prophylactic hemin: Panhematin used prophylactically is not prescribed concurrently with givosiran (continued therapy restriction added 1Q 2026)

Added in 1Q 2026

Requests for indications that are not FDA-approved and are not specifically addressed in this policy will not be authorized unless the provider submits sufficient documentation of efficacy and safety consistent with Centene off-label use requirements. See the off-label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), and CP.PMN.53 (Medicaid) for the documentation standards required to consider coverage of off-label indications.

The coding listings included in this policy are provided for informational purposes only. Inclusion or exclusion of any code does not guarantee coverage. Providers should rely on current professional coding guidance and payer billing rules when submitting claims.

Requests for non‑FDA approved indications that lack adequate documentation of efficacy and safety per the referenced off‑label use policies will be considered not authorized. Providers seeking coverage for off‑label uses must follow the documentation and evidentiary requirements outlined in the applicable off‑label policies referenced in this document.

Use of givosiran that does not meet the policy’s diagnostic confirmation and documentation requirements may be considered not medically necessary. Specifically, claims or prior authorization requests may be denied if diagnostic criteria (genetic testing or recently elevated urinary ALA/PBG), required clinical information (attack frequency or prior prophylactic hemin use), or mandatory documentation such as current body weight are not provided.

Coding and Test Thresholds

HCPCS CodesHCPCS

J0223

Injection, givosiran, 0.5 mg

HCPCS CodesHCPCS

J0223

Injection, givosiran, 0.5 mg

Urine ALA or PBG — diagnostic threshold

ThresholdUrine ALA or PBG concentration greater than four times the upper limit of normal on a random urine sample

Sample typeRandom urine sample (creatinine-correction variations may apply across labs)

PurposeDiagnostic confirmation of acute hepatic porphyria (AHP)

Recurrent porphyria attacks — coverage threshold

Coverage thresholdRecurrent porphyria attacks defined as 4 attacks per year (per 1Q 2026 revision)

Attack definitionAttack requires hospitalization, urgent healthcare visit, or intravenous administration of Panhematin

Provider Requirements, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Givlaari (givosiran). Initial approvals vary by line of business (Medicaid/HIM: 12 months; Commercial: 6 months or to the member's renewal date, whichever is longer). Claims may be denied for incorrect coding (e.g., HCPCS J0223) or failure to meet updated coverage criteria.

Prior authorization required for J0223 (givosiran)
Initial approval duration: Medicaid/HIM = 12 months; Commercial = 6 months or to member renewal date

Documentation Required

Required Documentation

Provider must submit documentation supporting that the member meets all approval criteria. Required documentation includes office chart notes, laboratory results, clinical information confirming diagnosis, and documentation of current body weight (kg). Absence of these documents may result in non-approval.

Office chart notes and clinical progress notes

Definitions and Contraindications

Acute hepatic porphyria (AHP) — definition & diagnostic confirmation

DefinitionAcute hepatic porphyria (AHP) is a group of disorders including acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALAD porphyria

Diagnostic confirmation methodsEither subtype-specific genetic testing (HMBS, CPOX, PPOX, or ALAD mutations) OR a documented ≥4-fold increase in urinary ALA or PBG on a random urine sample (per Appendix E)

Relevant abbreviationsAHP, AIP, HCP, VP, ALAD, ALA (5-aminolevulinic acid), PBG (porphobilinogen)

Contraindication — severe hypersensitivity to Givlaari

ContraindicationSevere hypersensitivity to Givlaari (givosiran); reactions have included anaphylaxis

Warnings

Background

Givosiran (Givlaari) is a small interfering RNA (siRNA) that targets aminolevulinate synthase 1 and is approved for treatment of adults with acute hepatic porphyria (AHP). Diagnosis for coverage purposes can be confirmed by subtype‑specific genetic testing or by a documented ≥4‑fold increase in urinary ALA or PBG on a random urine sample; policy updates have clarified that the urine sample must be collected within the past year.

Revision History and Policy Changes

2022-01-05revised

Revised confirmatory diagnostic criteria to allow either genetic testing OR elevated urinary ALA/PBG and clarified that ALA/PBG urine sample must be collected within the past year.

2023-02-23added

Added hepatologist to the list of prescribing specialties or consultants for givosiran.

2024-02-24added

Added requirement to document the member's current body weight (in kg) in the documentation criteria.

Policy Summary

PayerCentene

PolicyClinical Policy: Givosiran (Givlaari)

Policy CodePolicy CP.PHAR.457

Change TypeMaterial clinical and coverage revisions (diagnostic criteria, attack threshold, approval duration, concurrent therapy restriction).

Effective DateMar 1, 2020

Next Review Date

SourceLink

On This Page

Use in criteriaMeets initial approval when member has ≥4 attacks/year unless receiving prophylactic Panhematin

ALA/PBG specimen recency requirement

Recency requirementUrine ALA/PBG sample must have been collected within the past year

Acceptable evidenceDocumented ≥4-fold increase in urinary ALA or PBG on that recent random urine sample

RationaleClarified in 1Q 2022 review to allow either genetic testing or recent elevated ALA/PBG for diagnostic confirmation

Givosiran (0.5 mg) — HCPCS identifier

HCPCS codeJ0223

DescriptionInjection, givosiran, 0.5 mg

UseBilling code for givosiran (Givlaari) per policy coding section

Laboratory results (genetic testing reports OR urine ALA/PBG showing ≥4-fold increase within past year)

Documentation of current body weight (kg)

Step Therapy

Required Prior Therapy or Attack Threshold

Before initiating Givlaari, members must meet prior therapy or attack-threshold criteria: either be currently receiving prophylactic Panhematin therapy (regularly scheduled, e.g., once or twice weekly) or have experienced ≥4 porphyria attacks in the past year (attacks defined as requiring hospitalization, urgent healthcare visit, or IV Panhematin).

Acceptable entry criteria: prophylactic Panhematin OR ≥4 porphyria attacks/year
Porphyria attack definition: hospitalization, urgent visit, or IV Panhematin administration

Denial Risk

Concurrent Therapy Restriction

Concurrent prophylactic use of Panhematin with Givlaari is not allowed. Use of Panhematin to treat acute porphyria attacks while a member is receiving Givlaari is permissible.

Do not prescribe Panhematin prophylactically at the same time as Givlaari
Panhematin may be used acutely to treat breakthrough attacks during Givlaari therapy

Boxed warnings: none reported (per Appendix C)

Clinical actionDo not administer givosiran to patients with known severe hypersensitivity to the product

Recurrent porphyria attacks — policy definition (revised)

Coverage definitionRecurrent porphyria attacks for coverage purposes defined as 4 attacks per year (revised from ≥2 attacks in 6 months)

Effective revision dateChange made in the 1Q 2026 annual review per AGA guidelines

ImplicationThis threshold is used to determine eligibility for initial approval when not receiving prophylactic Panhematin

2026-02-26revisedLatest

Revised recurrent porphyria attack threshold to 4 attacks per year and added that prophylactic Panhematin must not be prescribed concurrently with givosiran; extended initial approval duration from 6 to 12 months.