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.”

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.

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