Alnylam completes rolling submission of NDA to the FDA and submits MAA to the European Medicines Agency for lumasiran for the treatment of primary hyperoxaluria Type 1.

Alnylam Pharmaceuticals, Inc. announced the completion of the rolling submission of a New Drug Application (NDA) to the FDA for lumasiran, an investigational RNAi therapeutic targeting glycolate oxidase (GO), in development for the treatment of primary hyperoxaluria type 1 (PH1). PH1 is an ultra-rare, life-threatening disease impacting the kidneys and other vital organs; it affects infants, children, and adults.

In the U.S., lumasiran has previously received Pediatric Rare Disease Designation, Orphan Drug Designation, and Breakthrough Therapy Designation for the treatment of PH1, based on data showing a substantial reduction in urinary oxalate, the key toxic metabolite responsible for the clinical manifestations of the disease.

The Company also announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for lumasiran for the treatment of PH1. Lumasiran has been granted Priority Medicines (PRIME) Designation by the EMA as well as Orphan Drug Designation in the European Union. Lumasiran has also been granted an accelerated assessment by the EMA which is awarded to medicines deemed to be of major public health interest and therapeutic innovation. Accelerated assessment potentially provides a reduced review timeline from 210 to 150 days once the MAA is filed and validated.

Comment: Primary Hyperoxaluria Type 1 (PH1) is an inborn error of metabolism. Specifically, PH1 is an autosomal recessive disorder of glyoxylate (oxoethanoate) metabolism, where hepatic detoxification of glyoxylate is impaired due to mutation of the AGXT gene, which encodes the liver peroxisomal alanine-glyoxylate aminotransferase (AGT) enzyme, resulting in excessive oxalate production. Excess oxalate (ethanedioate) in PH1 patients is unable to be fully excreted by the kidneys leading to the formation of recurrent kidney stones and the deposition of calcium oxalate crystals in the kidneys and urinary tract. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys and renal obstruction by calcium oxalate stones.