Background

Acute hepatic porphyria (AHP) is a rare disease with a prevalence of 5 to 10 cases/100,000 people in the U.S. and effects primarily females (age range 15 to 45 years). The induction of the enzyme amino levulinate synthase 1 (ALAS1) results in increased production and accumulation of toxic heme intermediates delta aminolevulinic acid and porphobilinogen in the plasma and urine. The accumulation of these toxic heme intermediates results in acute attacks characterized by severe abdominal pain, muscle weakness, seizures, psychiatric dysfunction, irreversible neurologic damage, and increased risk of hepatic malignancy.

Givosiran (Givlaari^®) is a double-stranded small interfering RNA that causes degradation of ALAS1 mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to decreased circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of acute hepatic porphyria.

Policy

1. Diagnosis of acute hepatic porphyria (i.e., acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, ALA dehydrase deficient porphyria)

AND

2. Patient has active disease with at least two documented porphyria attacks within the past 6 months

AND

3. Provider attestation documenting elevated urinary or plasma levels of one of the following within the past 12 months:

• • Porphobilinogen (PBG)
  • Delta-aminolevulinic acid (ALA)

AND

4. Patient has not had a liver transplant

AND

5. Prescribed by or in consultation with a gastroenterologist or a specialist with expertise in the diagnosis and management of acute hepatic porphyria

References

1. Bissell DM, Wang B. Acute Hepatic Porphyria. J Clin Transl Hepatol. Mar 2015; 3(1): 17-26. PMID 26357631
2. Wang B, Rudnick S, Cengia B, et al. Acute Hepatic Porphyrias: Review and Recent Progress. Hepatol Commun. Feb 2019; 3(2): 193-206. PMID 30766957
3. Balwani M, Sardh E, Ventura P, et al. Phase 3 Trial of RNAi TherapeuticGivosiran for Acute Intermittent Porphyria. N Engl J Med. Jun 11, 2020; 382(24): 2289-2301. PMID 32521132
4. Ventura P, Bonkovsky HL, Gouya L, et al. Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study. Liver Int. Jan 2022; 42(1): 161-172. PMID 34717041
5. Prescribing Label: Givlaari (givosiran) injection, for subcutaneous use. Initial U.S. Approval: 2019. Available at https://www.alnylam.com/sites/default/files/pdfs/GIVLAARI-Prescribing-Information.pdf. Accessed May 3, 2023.
6. Wang B, Bonkovsky HL, Lim JK, et al. AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review. Gastroenterology. Mar 2023; 164(3): 484-491. PMID 36642627
7. National Institute for Health and Care Excellence. Givosiran for treating acute hepatic porphyria. Highly specialized technologies guidance. Reference number:HST16. Published: 24 November 2021. Available at https://www.nice.org.uk/guidance/hst16. Accessed May 3, 2023.

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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