Currently Enrolling Trials
Givlaari (givosiran) is an aminolevulinate synthase 1-directed small interfering RNA.
Givlaari is specifically indicated for the treatment of adults with acute hepatic porphyria.
Givlaari is supplied as an injection for subcutaneous administration. The recommended dose of Givlaari is 2.5 mg/kg administered via subcutaneous injection once monthly. Dosing is based on actual body weight. If a dose is missed, administer Givlaari as soon as possible. Resume dosing at monthly intervals following administration of the missed dose.
Mechanism of Action
Givlaari (givosiran) is a double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing the elevated levels of liver ALAS1 mRNA. This leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP.
Adverse effects associated with the use of Givlaari may include, but are not limited to, the following:
- injection site reactions
Clinical Trial Results
The FDA approval of Givlaari was based on positive results from the phase 3 ENVISION study. The randomized, double-blind, placebo-controlled, multinational study enrolled 94 patients with AHP at 36 study sites in 18 countries. The patients on Givlaari experienced 70% fewer porphyria attacks compared to placebo. Givlarri also resulted in a similar reduction in intravenous hemin use, as well as reductions in urinary aminolevulinic acid (ALA), and urinary porphobilinogen (PBG).