An RNA interference therapy (givosiran) targeting ALAS1 reduced the rate of attacks and improved other disease manifestations in patients with acute intermittent porphyria, the most common subtype of acute hepatic porphyria. A total of 94 patients were randomly assigned either givosiran (n = 48) or placebo (n = 46) in a phase III trial. In 89 patients with acute intermittent porphyria, the mean annualized attack rate was significantly lower in the givosiran group than the placebo group (decreased by 74%, P < 0.001; 3.2 versus 12.5). Other disease manifestations (including pain) also improved in the treatment group. However, a higher frequency of hepatic and renal adverse events was observed in the givosiran group than the placebo group. Givosiran is now approved by the FDA and the European Medicines Agency for adults with acute hepatic porphyria.
Balwani, M. et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent porphyria. N. Engl. J. Med. 382, 2289–2301 (2020)
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Ray, K. Interfering with acute intermittent porphyria. Nat Rev Gastroenterol Hepatol 17, 452 (2020). https://doi.org/10.1038/s41575-020-0335-3