Givosiran

Givosiran, sold under the brand name Givlaari, is a subcutaneously administered RNA interference (RNAi) therapeutic developed by Alnylam Pharmaceuticals for the treatment of acute hepatic porphyrias (AHP). It is a GalNAc-conjugated small interfering RNA that targets hepatic aminolevulinate synthase 1 (ALAS1), the first enzyme in hepatic heme synthesis. By silencing ALAS1 in the liver, givosiran lowers hepatic production of aminolevulinic acid (ALA) and porphyrin precursors that accumulate during acute attacks, reducing systemic neurovisceral symptoms.

Givosiran is indicated for adults and for pediatric patients aged 12 years and older with acute hepatic porphyrias to reduce the frequency of acute attacks requiring hospitalization, urgent care visits, or treatment with hemin. It is administered by subcutaneous injection, typically once monthly, with dosing guided by labeling and patient response.

Efficacy data come from the ENVISION Phase 3 trial, which demonstrated a significant reduction in the annualized rate of porphyria attacks and improvement in biochemical markers such as ALA levels, compared with placebo. These results supported regulatory approval in the United States and later in the European Union.

Common adverse events observed in trials include nausea, injection-site reactions, and flu-like symptoms, along with laboratory abnormalities such as elevations in hepatic transaminases. Clinicians monitor liver function and renal function during treatment, and patients are advised to report signs of hypersensitivity or liver injury.

Givosiran received FDA approval in 2019 and subsequent approvals in other regions, and is part of the set of therapies targeting hepatic porphyrias.