ModifiedmhnPolicy CP.PHAR.457

Givosiran (Givlaari) for acute hepatic porphyria

Defines medical necessity and utilization management criteria for givosiran (Givlaari) for members with acute hepatic porphyria across commercial, HIM, and Medicaid lines of business. Applies to providers requesting prior authorization for treatment and continuation of therapy.

Policy Summary

Payermhn

PolicyGivosiran (Givlaari) for acute hepatic porphyria

Policy CodePolicy CP.PHAR.457

Change TypeCriteria revised and diagnostic/ documentation updates

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with confirmatory diagnostic evidence (genetic test or urine ALA/PBG within 1 year), current body weight, attack history, and prescriber specialty to support approval.

SourceLink

POLICY UPDATE CHANGES

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

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

Documentation of member's current body weight (in kg) was added as a required criterion.

Added hepatologist as a specialty able to prescribe or be in consultation with.

18minimum age for coverage

4/yrattack frequency threshold

2.5 mg/kgmaximum monthly dose

12 mo

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initial approval (Medicaid/HIM)

Coverage Criteria for Givosiran (Givlaari)

inv-01: Initial Therapy

Covered when ALL of the following are met

Initial Approval for AHP: 1) Diagnosis of acute hepatic porphyria (AHP: AIP, HCP, VP, or ALAD porphyria) confirmed by either: (a) genetic testing positive for the AHP-associated mutation (AIP: HMBS/PBGD; HCP: CPOX; VP: PPOX; ALAD porphyria: ALAD) OR (b) history of at least a four-fold increase of 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) One of the following: (a) member is currently receiving prophylactic Panhematin therapy (e.g., once or twice weekly on a regular basis) OR (b) member has experienced ≥ 4 porphyria attacks per year (attack defined as requirement of hospitalization, urgent healthcare visit, or intravenous Panhematin); 5) Panhematin, when used as prophylaxis, is not prescribed concurrently with Givlaari (use of Panhematin for treatment of acute attacks while taking Givlaari is allowed); 6) Documentation of member's current body weight (kg); 7) Dose does not exceed 2.5 mg/kg once monthly.see node text

inv-02: Continuation Therapy

Covered when ALL of the following are met

Continuation for AHP: 1) Member currently receiving medication via Centene benefit or previously met initial approval criteria or is enrolled in a state/product with continuity of care; 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 at home OR (b) if member was receiving prophylactic Panhematin prior to Givlaari initiation, no increase in porphyria attacks requiring hospitalization, urgent healthcare visit, or IV Panhematin administration at home; 3) Panhematin, when used as prophylaxis, is not prescribed concurrently with Givlaari (use of Panhematin for acute attacks while on Givlaari is permitted); 4) Documentation of member's current body weight (kg); 5) If request is for a dose increase, new dose does not exceed 2.5 mg/kg once monthly.see node text

inv-03: Initial and Continued Therapy Criteria

Covered when ALL of the following are met

Confirmatory diagnosis: Member has confirmatory evidence of acute hepatic porphyria defined as either genetic testing positive for an AHP-associated mutation OR elevated urine ALA/PBG with the urine sample collected within the past year.

Revised 1Q2022 to allow either genetic or biochemical confirmation.

Attack frequency: Member experiences recurrent porphyria attacks meeting the revised threshold of 4 attacks per year (per AGA guidelines).4 attacks per year

Revised in 1Q2026.

Documentation: Prescriber documents member's current body weight (kg) and relevant diagnostic data in the medical record.

Weight documentation added in 1Q2024.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the request includes sufficient documentation of efficacy and safety in accordance with applicable off‑label use policies (see CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage.

Panhematin used as prophylaxis must not be prescribed concurrently with Givlaari for continued therapy. Use of Panhematin for treatment of acute attacks while a member is receiving Givlaari is permitted, but concurrent prophylactic administration with Givlaari is prohibited per the revised continued therapy criteria.

Requests for indications that are not FDA‑approved and are not addressed by this policy will be denied unless the requester provides sufficient documentation of efficacy and safety consistent with the plan's off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or other acceptable evidence of coverage.

The inclusion of an HCPCS code in this policy (for example, J0223 = Injection, givosiran, 0.5 mg) is for informational purposes only and does not guarantee coverage. Services billed using listed codes must meet the policy's medical necessity criteria and current professional coding guidance to be eligible for reimbursement.

Coding and Diagnostic Criteria

HCPCS Codes referencedHCPCS

J0223

Injection, givosiran, 0.5 mg

HCPCS CodesHCPCS

J0223

Injection, givosiran, 0.5 mg

ALA or PBG elevation — diagnostic threshold

ThresholdConcentrations of urinary ALA or PBG greater than four times the upper limit of normal in a random urine sample establish the diagnosis of AHP.

Sample typeRandom (spot) urine sample; reporting may vary across laboratories (creatinine-corrected or not).

Use for confirmationA ≥4-fold increase may be used as biochemical confirmation when genetic testing is unavailable or non-diagnostic.

Recurrent porphyria attacks — attack frequency threshold

ThresholdRecurrent porphyria attacks defined as 4 attacks per year (per AGA guidelines).

Attack definition

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Givlaari (givosiran). Providers must request prior authorization per the member's health plan prior to initiation. Include documentation that the member meets the clinical criteria (diagnosis confirmation, specialty involvement, age, attack history or prophylactic Panhematin status) and the requested dose (mg/kg) and current body weight in kg.

Prior authorization required before initiation
Prescriber: gastroenterologist, hematologist, hepatologist, or neurologist (or in consultation)
Include current body weight (kg) and proposed dose; dose limit: ≤ 2.5 mg/kg once monthly

Documentation Required

Documentation Required to Support Approval

Submit office chart notes, lab results (including genetic testing results or urine ALA/PBG showing ≥4-fold increase within the past year), infusion records or hospitalization/urgent visit documentation and any notes showing response to therapy. Failure to submit adequate clinical documentation supporting that the member meets the approval criteria may result in denial or delay.

Background

Givosiran (Givlaari) is a small interfering RNA (siRNA) therapeutic directed to aminolevulinate synthase 1 for the treatment of adults with acute hepatic porphyria (AHP). Coverage under this policy is limited to members who meet the specified diagnostic confirmation (either genetic testing positive for an AHP‑associated mutation or elevated urine ALA/PBG with the sample collected within the past year), age, specialty prescriber requirements, attack frequency or prophylactic Panhematin use criteria, documentation of current body weight in kilograms, and dosing not to exceed 2.5 mg/kg once monthly. Recent policy revisions align the attack frequency threshold with AGA guidance (4 attacks per year), prohibit concurrent prophylactic Panhematin with Givlaari for continued therapy, and extend maintenance approval duration.

Definitions and Administration

Acute hepatic porphyria (AHP) — definition and subtypes

DefinitionAcute hepatic porphyria (AHP) is a group of metabolic disorders including acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA dehydratase-deficiency (ALAD) porphyria.

Diagnostic basisAHP is diagnosed by disease-specific gene mutations or by a ≥4-fold increase in urinary ALA or PBG.

Clinical significanceClinical attacks can require hospitalization, urgent care, or intravenous hemin (Panhematin).

Missed dose handling — guidance for missed Givlaari doses

General guidanceIf a scheduled monthly dose is missed, administer Givlaari as soon as possible and then resume monthly dosing thereafter.

Dose resumption

Policy Summary

Payermhn

PolicyGivosiran (Givlaari) for acute hepatic porphyria

Policy CodePolicy CP.PHAR.457

Change TypeCriteria revised and diagnostic/ documentation updates

Effective DateMar 1, 2020

Next Review Date

SourceLink

On This Page

Concomitant therapy: Panhematin, when used as prophylaxis, is not prescribed concurrently with Givlaari for continued therapy.

Added to continued therapy criteria in 1Q2026.

Attack defined as requirement of hospitalization, urgent healthcare visit, or intravenous administration of Panhematin.

ContextRevised from prior criterion of ≥2 attacks in 6 months to align with AGA guidance (1Q2026 update).

Confirmatory diagnostic criteria — genetic testing OR elevated urine ALA/PBG (recency requirement)

Acceptable confirmatory evidenceEither genetic testing positive for an AHP-associated mutation OR elevated urine ALA/PBG (biochemical).

Genetic testing specificsGenetic confirmation includes HMBS mutation for AIP, CPOX for HCP, PPOX for VP, or ALAD mutation for ALAD porphyria.

Recency requirement for urine ALA/PBGIf using urine ALA/PBG, the random urine sample must have been collected within the past year.

Required documentation: genetic test report OR urine ALA/PBG result (random urine within past year)
Clinical progress notes documenting attack frequency and response to therapy
Documentation if member previously received prophylactic Panhematin

Denial Risk

Documentation / Criteria Not Met — Denial Risk

If required criteria or documentation are not provided (diagnostic confirmation, attack frequency, specialty prescriber/consultation, current body weight, or evidence that prophylactic Panhematin is not being given concurrently), the prior authorization request may be denied. Lack of required supporting records (office notes, labs, or hospitalization/IV treatment records) is a common reason for denial.

Missing genetic testing or recent (≤1 year) ALA/PBG urine result may trigger denial
Absence of documentation showing ≥4 porphyria attacks per year or evidence of prophylactic Panhematin status may trigger denial

Billing Rule

Coding and Coverage Mismatch Risk

Claims may be denied or delayed if coding does not match services rendered or policy guidance. Use the appropriate HCPCS code for givosiran (J0223) and ensure diagnosis coding supports acute hepatic porphyria and aligns with submitted clinical documentation.

HCPCS: J0223 — Injection, givosiran, 0.5 mg (informational)
Ensure ICD-10 diagnosis codes correspond to acute hepatic porphyria and the supporting documentation

Documentation Required

Attack Frequency and Concomitant Therapy Documentation

Providers must document attack frequency to meet the coverage threshold: member must have experienced 4 or more porphyria attacks per year (defined as hospitalization, urgent healthcare visit, or IV Panhematin administration) unless member is currently receiving prophylactic Panhematin and meets continuity provisions. For continued therapy, show decreased attack frequency or, if previously on prophylactic Panhematin, no increase in attacks after switching to Givlaari.

Attack frequency requirement: ≥4 porphyria attacks per year
Acceptable attack evidence: hospitalizations, urgent visits, or IV Panhematin administration records
For continuation: documentation of clinical response (reduced attacks) or stability if transitioning from prophylactic Panhematin

Prior Authorization

Concomitant Therapy Restriction — Prophylactic Panhematin Prohibited

Panhematin must not be used as prophylactic therapy concurrently with Givlaari. Use of Panhematin for acute porphyria attacks while receiving Givlaari is acceptable and should be documented. Explicitly indicate whether Panhematin is being used prophylactically; requests showing concurrent prophylactic Panhematin use will not meet criteria.

Prophylactic Panhematin concurrently with Givlaari is prohibited
Use of Panhematin for acute attacks while on Givlaari is permitted and should be documented

After administering the missed dose, continue subsequent doses on the original monthly schedule (i.e., monthly intervals following the missed dose).

Dose modification contextDose adjustments for adverse reactions (e.g., transaminase elevation) are handled separately; missed-dose guidance does not alter dose-modification rules.