Overview

This document addresses the use of Givlaari (givosiran), aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA indicated for the treatment of adults with acute hepatic porphyria (AHP). Porphyria is a group of eight genetic disorders that cause defective production of heme, the oxygen-carrying component of red blood cells. Acute hepatic porphyria is a form of porphyria with 4 subtypes: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA dehydratase-deficiency porphyria (ADP). In AHP, defective enzymes in the heme biosynthesis pathway allow aminolevulinic acid (ALA) and other neurotoxic heme intermediates to accumulate. This accumulation can trigger a porphyria attack. AHP occurs primarily in women and has an onset in young adulthood. Porphyria attacks are characterized by severe abdominal and neuropathic pain, many nonspecific symptoms, hypertension, hyponatremia, and red urine. Attacks can last for days and can be life-threatening. It can be triggered or exacerbated by factors that increase ALAS1 activity and ALA accumulation. This includes inadequate carbohydrate intake, stress, pain, female hormonal changes, smoking, excessive alcohol use, and drugs or substances that induce ALAS1 activity. Long-term complications of AHP include liver disease, hepatocellular carcinoma, chronic kidney disease, and hypertension. Givlaari is the first FDA-approved treatment that prevents attacks of acute hepatic porphyria. It works by muting ALAS1 via RNA interference through monthly subcutaneous injections administered by a healthcare professional. Givlaari is not approved for other forms of porphyria, such as cutaneous forms of porphyria, where standard treatment typically includes regularly scheduled phlebotomies. Prior to Givlaari, the only approved treatment for recurrent porphyria attacks from AHP was the administration of Panhematin (hemin), an intravenous infusion, along with carbohydrate loading and supportive care. Although it has been known to be used off-label for preventative therapy, Panhematin is only FDA-approved for management of acute attacks.

Clinical criteria

Overview

Coding

Document history

References

Clinical Criteria

When a drug is being reviewed for coverage under a member’s medical benefit plan or is otherwise subject to clinical review (including prior authorization), the following criteria will be used to determine whether the drug meets any applicable medical necessity requirements for the intended/prescribed purpose.

Givlaari (givosiran)

Requests for initiation of Givlaari (givosiran) may be approved if the following criteria are met:

1. Individual is 18 years of age or older; AND
2. Individual has a diagnosis of acute hepatic porphyria, and confirmation of one of the following subtypes (APF):
   • Acute intermittent porphyria (AIP); OR
   • Hereditary coproporphyria (HCP), OR
   • Variegate porphyria (VP); OR
   • ALA dehydratase-deficiency porphyria (ADP); AND
3. Documentation is provided that individual has an elevated urinary or plasma porphobilinogen (PBG) or delta-aminolevulinic acid (ALA) within the past year (Balwani 2019); AND
4. Individual meets one of the following criteria:
   • Individual has active symptomatic disease, with at least two porphyria attacks within the last six months, and documentation is provided (Balwani 2019); OR
   • Individual is currently on prophylactic hemin treatment due to history of severe or frequent porphyria attacks.

Requests for continuation of Givlaari (givosiran) may be approved if the following criteria are met:

1. Individual is 18 years of age or older;
2. The individual continues to meet all initial approval criteria.

Documentation is provided that individual has experienced a clinical response to therapy (for example, a reduction in the number of porphyria attacks, or a reduction in hemin requirements for acute attacks); AND

Individual does not have severe or clinically significant transaminase elevations, defined as alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (Balwani 2019).

Givlaari (givosiran) may not be approved for the following (NCT03338816):

1. Concurrent use of prophylactic hemin treatment with Givlaari (givosiran); OR
2. Liver transplantation is anticipated; OR
3. Individual has a history of recurrent pancreatitis; OR
4. Individual is requesting for other forms of porphyria, such as cutaneous porphyrias (for example, porphyria cutanea tarda [PCT]); OR
5. When the above criteria are not met and for all other indications.

Approval Duration:

• Initial Requests: 6 months
• Maintenance Requests: 12 months

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

J0223
Injection, givosiran, 0.5 mg

ICD-10 Diagnosis

E80.20-E80.29
Hereditary porphyria
Z29.9
Encounter for prophylactic measures, unspecified

Document History

Reviewed: 12/11/2023