Givosiran, sold under the brand name Givlaari, is a medication used for the treatment of adults with acute hepatic porphyria.^[3][6][7][8] Givosiran is a small interfering RNA (siRNA) directed towards delta-aminolevulinate synthase 1 (ALAS1),^[9] an important enzyme in the production of heme.

The most common side effects include nausea and injection site reactions.^[8]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[10]

Medical uses

Givosiran is indicated for the treatment of adults with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme (which helps bind oxygen in the blood).^[3][7]

History

In November 2019, givosiran was approved in the United States for the treatment of adults with acute hepatic porphyria (AHP).^[7][11]

Efficacy was evaluated in ENVISION (NCT03338816), a randomized, double‑blind, placebo‑controlled, multinational trial enrolling 94 participants with acute hepatic porphyria.^[8] Participants were randomized (1:1) to receive once monthly subcutaneous injections of givosiran 2.5 mg/kg or placebo during a six‑month double‑blind period.^[8] The performance of givosiran was measured by the rate of porphyria attacks that required hospitalizations, urgent health care visits or intravenous infusion of hemin at home.^[7] Participants who received givosiran experienced 70% fewer porphyria attacks compared to patients receiving a placebo.^[7]

The U.S. Food and Drug Administration (FDA) granted the application for givosiran breakthrough therapy designation, priority review designation, and orphan drug designation.^[7][8] The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals.^[7]