Givosiran (Givlaari™) is an aminolevulinate synthase 1 (ALAS1)-directed small 
interfering RNA (siRNA) covalently linked to a ligand to enable specific 
delivery of the siRNA to hepatocytes. This results in downregulation of ALAS1 
mRNA and prevents accumulation of neurotoxic δ-aminolevulinic acid and 
porphobilinogen levels that are associated with acute porphyria attacks. 
Givosiran is being developed by Alnylam Pharmaceuticals for the treatment of 
acute hepatic porphyria (AHP). In November 2019, givosiran was approved in the 
USA for the treatment of adults with AHP based on the positive results from the 
multinational, phase III ENVISION trial. In the EU, givosiran received a 
positive opinion in January 2020 for the treatment of AHP in adults and 
adolescents aged 12 years and older. This article summarizes the milestones in 
the development of givosiran leading to this first approval for the treatment of 
adults with AHP.