Givosiran for Acute Hepatic Porphyria

Acute hepatic porphyria (AHP) is a rare disease with a prevalence of 5 to 10 cases/100,000 people in the US and effects primarily females (age range 15 to 45 years). The induction of the enzyme aminolevulinate 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.