Givlaari (givosiran)

POLICY NUMBER

L.5.01.553

Givlaari (givosiran)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Acute hepatic porphyria (AHP) is an inherited disorder due to a pathogenic mutation that causes a deficiency in hepatic heme biosynthesis. This can lead to an accumulation of the potentially toxic porphyrin precursors aminolevulinic acid (ALA) and porphobilinogen (PBG). Symptoms usually occur as episodic, acute neurovisceral attacks, which may be sporadic or recurrent and potentially life-threatening. Symptoms may include severe abdominal pain, nausea, vomiting, tachycardia, hypertension, hyponatremia, mental status changes, muscle weakness, seizures, and change in urine color to red/brown. The four types of AHP disorders are acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA dehydratase porphyria (ADP).

Givosiran is a small, interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing elevated levels of liver ALAS1 mRNA. This leads to a reduction in circulating levels of ALA and PBG, the neurotoxic intermediates associated with disease manifestations of AHP. Givlaari (givosiran) is indicated for the treatment of adults with acute hepatic porphyria (AHP).

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Criteria

Givlaari (givosiran) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is ≥18 years of age

2. The individual has a definitive diagnosis of acute hepatic porphyria as evidenced by at least ONE of the following:

   1. Elevated urine or plasma PBG or ALA level within the past 12 months; OR

   2. Presence of a mutation in an affected gene;

1. The individual has evidence of active disease with a history of ONE of the following within the previous 6 months:

   1. At least 2 documented porphyria attacks

      (i.e., requirement of hospitalization, urgent healthcare visit or intravenous administration of hemin); OR

   2. One severe attack with CNS involvement (e.g., hallucinations, seizures, etc.)

2. Individuals currently receiving prophylactic intravenous hemin therapy will discontinue hemin within 3 to 6 months of initiation of the requested agent;

3. The individual will avoid known triggers of porphyria attacks (i.e., alcohol, smoking, exogenous hormones, hypocaloric diet/fasting, certain medications such as barbiturates, hydantoins, sulfa-antibiotics, anti-epileptics, etc.);

4. The individual has not had or is not anticipating a liver transplant;

5. The medication is prescribed by, or in consultation with, a specialist in the treatment of acute hepatic porphyria (e.g., hematologist, hepatologist);

6. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

7. The prescribed dosage is within the program quantity limits limits based on FDA approved labeled dosage.

Length of approval: 6 months

Renewal Criteria

Givlaari (givosiran) will be approved for renewal when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical response/improvement (i.e., decrease in frequency of acute porphyria attacks, hospitalizations, urgent care visits, and/or decrease in requirement of intravenous hemin infusions for acute attacks);

3. The individual has a reduction/normalization of biochemical markers (i.e., ALA, PBG) compared to baseline;

4. The individual will not use in combination with prophylactic intravenous hemin therapy;

5. Liver transplantation is not anticipated and has not occurred since the previous authorization;

6. The medication is prescribed by, or in consultation with, a specialist in the treatment of acute hepatic porphyria (e.g., hematologist, hepatologist);

7. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

8. The prescribed dosage is within the program quantity limits limits based on FDA approved labeled dosage.

Length of approval: 12 months

Renewal Criteria

Givlaari (givosiran) will be approved for renewal when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical response/improvement (i.e., decrease in frequency of acute porphyria attacks, hospitalizations, urgent care visits, and/or decrease in requirement of intravenous hemin infusions for acute attacks);

3. The individual has a reduction/normalization of biochemical markers (i.e., ALA, PBG) compared to baseline;

4. The individual will not use in combination with prophylactic intravenous hemin therapy;

5. Liver transplantation is not anticipated and has not occurred since the previous authorization;

6. The medication is prescribed by, or in consultation with, a specialist in the treatment of acute hepatic porphyria (e.g., hematologist, hepatologist);

7. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

8. The prescribed dosage is within the program quantity limits limits based on FDA approved labeled dosage.

Length of approval: 12 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

05/01/2020: New policy added.

06/26/2020: Code Reference section updated to add new HCPCS code J0223, effective 07/01/2020.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy updated to change "Givlaari (givosiran sodium)" to "Givlaari (givosiran)." Policy description updated regarding acute hepatic porphyria and indications for Givlaari (givosiran). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding diagnosis of acute hepatic porphyria, known triggers of porphyria attacks, liver transplant, contraindications to therapy, and dose requirements. Renewal criteria revised regarding the following: 1) requirement that the individual has been previously approved for the requested agent through the BCBSMS PA process; 2) documented clinical response/improvement; 3) liver transplantation; 4) prescriber requirement; 5) contraindications to therapy; and 6) dose requirements. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders." Sources updated.

SOURCE(S)

1. Balwani M, Wang B, Yazici C, Anderson KE, Bissell DM, et al. Acute HepaticPorphyrias: Recommendations for Evaluation and Long Term Management Hepatology. 2017; 66(4): 1314-1322.

2. Glivlaari prescribing information. Alnylam Pharmaceuticals, Inc. April 2024. Accessed March 2025.

3. Stölzel U, Doss MO, Schuppan D, et al. Clinical guide and update on porphyrias. Gastroenterology 2019;157(2):365-81. Available at: https://www.gastrojournal.org/article/S0016-5085(19)40883-4/pdf.

4. Wang B, Bonkovsky HL, Lim JK, Balwani M. AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review. Gastroenterology 2023; 164:484.

5. Wang B, Rudnick Sean, Cegia B, Bonkovsky HL. Acute Hepatic Porphyrias: Review and Recent Progress. Hepatology Communications 2019; 3:193?206.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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