Givlaari (givosiran) Policy

Coverage Summary

Coverage stance: covered_with_criteria. Scope: Medical-benefit pharmacy policy defining prior-authorization criteria for Givlaari (givosiran) for adults with acute hepatic porphyria (AHP). Effective date: 2024-07-01; Last review: 2024-01-26. Givlaari (givosiran) is approved for the treatment of adults with AHP and is covered under this policy when the prior authorization criteria (including age, diagnostic confirmation, recurrent-attack criteria or current prophylactic hemin use, prescriber specialty, exclusions, and dosing limits) are met.

Initial Authorization — Acute Hepatic Porphyria (AHP)

Initial Authorization - Acute Hepatic Porphyria (AHP)

Covered when ALL of the following are met:

ALL of the following

Member is at least 18 years of age
Member has a documented diagnosis of Acute Hepatic Porphyria with one of the following types: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), or aminolevulinic acid dehydratase deficiency porphyria (ADP)
Prescriber specialty is gastroenterologist or hepatologist
policy history indicates addition of neurology and hematology to accepted prescriber specialties (12/20/2022)
Diagnosis must be confirmed by labs showing an elevated level of urinary ALA or PBG (elevated within the past year)Elevated urinary ALA or PBG within past year
document text notes a numeric typographic error; policy requires biochemical confirmation (added 12/20/2022)
ONE of
- At least 4 porphyria attacks in the past year requiring hospitalization, urgent care visit, or intravenous hemin administration at home>= 4 attacks in past year
  Recurrent attacks definition per guideline
- Member is currently receiving off-label hemin treatment for attack prophylaxis
  Patients already receiving prophylactic hemin may qualify without meeting recurrent attack definition (01/26/2024)
Chart notes include documentation of active recurrent porphyria attacks (as above)
Member has been assessed for possible attack triggers (e.g., certain drugs, smoking, alcohol, or low carbohydrate diets) and counseled to avoid these potential causative factors
Added trigger avoidance criterion (12/20/2022)
Exclusions
- Member does NOT have prior or anticipated liver transplant
  liver transplant exclusion added (12/20/2022)
- Member does NOT have active HIV, hepatitis B, or hepatitis C infection
Member will not be receiving concomitant prophylactic treatment with IV hemin (Panhematin). Note: Hemin for treatment of acute attacks is permitted
Concomitant prophylactic IV hemin prohibited; acute-use hemin permitted

Prior Authorization

Obtain prior authorization

Submit a prior authorization request to the medical benefit reviewer with documentation demonstrating that the patient meets all initial or reauthorization criteria for Givlaari (givosiran).

Include prescriber specialty (gastroenterologist or hepatologist; neurology and hematology were added to accepted specialties per policy history).
Note: Givlaari is a medical benefit and prior authorization is required.

Reauthorization (Continuation) Criteria

For approval of additional therapy, ALL of the following must be met:

ALL of the following

Chart notes document reduced number of porphyria attacks requiring hospitalization, urgent care, or Panhematin use
Reauthorization requirement
ANY of the following
- Chart notes document reduced severity of attack symptoms such as pain and decreased opioid use
Member is not using Panhematin for attack prophylaxis (Panhematin allowed for acute use only)

Quantity, Approval Duration, and Not Medically Necessary

ALL of the following

Dose/Quantity limit: Dosage allowed/Quantity limit: 2.5 mg/kg subcutaneous injection once monthly2.5 mg/kg once monthly
Initial duration: Initial approval duration: 6 months if initial criteria met6 months
Reauthorization duration: Reauthorization approval duration: 12 months if reauthorization criteria met12 months

Exclusions / Denial Risk

Exclusion Criteria

Member does NOT have prior or anticipated liver transplant
liver transplant exclusion added 12/20/2022
Member does NOT have active HIV, hepatitis B, or hepatitis C infection
Member will not be receiving concomitant prophylactic IV hemin (Panhematin)
Hem in for acute attacks is permitted

Denial Risk

Provider Actions & Documentation Requirements

Documentation Required

Provide diagnostic biochemical confirmation

Include laboratory confirmation of AHP by submitting urinary ALA or PBG results obtained within the past year to confirm the diagnosis.

Policy threshold: elevated urinary ALA or PBG within the past year (policy text lists “24 times the upper limit of normal” but policy history indicates diagnostic confirmation criterion was added and the BRIEF notes this appears to be a typographic error; intended threshold is ≥2× ULN).

Documentation Required

Assess and document trigger counseling

Document that the patient has been assessed for potential porphyria attack triggers and that counseling was provided to avoid those triggers.

Assess and document counseling regarding certain drugs, smoking, alcohol, and low‑carbohydrate diets as potential triggers.

Applicable Codes & Benefit

Benefit Type / Prior Authorizationmixed

Medical benefit	Givlaari (givosiran) classified as Medical benefit under Arkansas PASSE
Prior Authorization Required	Policy requires prior authorization

Clinical Evidence

In the pivotal phase 3 ENVISION trial, patients treated with givosiran experienced an average of 70% fewer porphyria attacks than placebo. Historically, intravenous hemin (Panhematin) has been the mainstay for treating acute attacks and has been used off-label for attack prevention/prophylaxis.

Background

Givlaari (givosiran) is an ALAS1-directed small interfering RNA (siRNA) that causes degradation of ALAS1 mRNA in hepatocytes to lower ALAS1 and reduce accumulation of the neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG). It is FDA-approved for adults with acute hepatic porphyria (AHP). Historically, intravenous hemin (Panhematin) has been used as the mainstay treatment for acute attacks and has also been used off-label for prophylaxis in patients with recurrent attacks.

Key Thresholds for Givlaari (givosiran)

Age>= 18 years

Diagnostic biochemical confirmationElevated urinary ALA or PBG within the past year (document notes '24 times the upper limit of normal' — typographic error; intended elevated ALA/PBG)

Recurrent attacks>= 4 attacks in the past year requiring hospitalization, urgent care, or IV hemin at home (or current prophylactic hemin)

Dose2.5 mg/kg subcutaneous once monthly

Definitions

Recurrent attacks: at least 4 attacks in the past year requiring hospitalization, urgent care, or intravenous hemin administration at home, or current prophylactic hemin use.

Diagnostic confirmation: elevated urinary ALA or PBG within the past year (documented biochemical confirmation).

Revision History

04/23/2020initial_policy

Initial policy created (New policy for Givlaari).

12/20/2022material_change

Material updates: transferred to new template, updated J code and references, added diagnostic confirmation via biochemical testing (urinary ALA/PBG criterion), added trigger avoidance criterion, and expanded accepted prescriber specialties to include neurology and hematology.

01/26/2024material_changeLatest