The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for givosiran (Alnylam) for the treatment of acute hepatic porphyria (AHP).

AHP is a rare, genetic disease characterized by episodic and potentially life-threatening attacks. The disease is comprised of 4 subtypes that result from genetic defects affecting the heme biosynthesis pathway in the liver; this causes the accumulation of neurotoxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG). Givosiran is a subcutaneously-administered RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1); treatment is expected to lower induced liver ALAS1 levels and decrease these intermediates.

Givosiran was previously granted Breakthrough Therapy designation and Orphan Drug designation from the FDA. The Company submitted an NDA in June 2019 based on data from the ENVISION phase 3 study. The study evaluated the efficacy and safety of givosiran in 94 patients with a documented diagnosis of AHP. Results of the study showed that treatment with givosiran led to a significant reduction in the annualized rate of composite porphyria attacks compared with placebo (P <.00000001).

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With regard to safety, adverse events reported in >10% of givosiran-treated patients included nausea, injection site reactions, chronic kidney disease (all in patients with renal dysfunction at baseline) and fatigue.


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A Prescription Drug User Fee Act (PDUFA) action date for the NDA has been set for February 4, 2020.

For more information visit alnylam.com.