The New Drug Application (NDA) for givosiran (Alnylam), an investigational treatment for acute hepatic porphyria (AHP), has been submitted to the Food and Drug Administration (FDA).

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.

The NDA submission was supported by data from the ENVISION phase 3 study which evaluated the safety and efficacy 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). 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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“We’re very pleased to have completed our NDA filing for givosiran, just 90 days since reporting our positive topline ENVISION phase 3 study results, consistent with our commitment to bring givosiran to patients as rapidly as possible,” said Akin Akinc, PhD, Vice President and General Manager, Givosiran Program at Alnylam. “[…] We look forward to working with the FDA and other global regulatory agencies to bring this medicine to patients.”


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Currently, there are no approved treatments to prevent or treat AHP. The FDA had previously granted givosiran Breakthrough Therapy designation and Orphan Drug designation for AHP.

For more information visit alnylam.com.