RARE Daily

FDA Grants Alnylam Priority Review for Experimental PH1 Treatment

May 26, 2020

Rare Daily Staff

The U.S. Food and Drug Administration has accepted Alnylam Pharmaceuticals’ New Drug Application for its experimental RNAi therapeutic lumasiran for the treatment of primary hyperoxaluria type 1 and granted it Priority Review.

Priority review is granted to drugs that treat a serious condition and if approved would provide a significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. The FDA is expected to act on the application by December 3, 2020 and has indicated that they are not currently planning an advisory committee meeting as part of the NDA review.

Primary hyperoxaluria type 1 (PH1) is an ultra-rare disease in which excessive oxalate production results in the deposition of calcium oxalate crystals in the kidneys and urinary tract, which can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and urinary obstruction by calcium oxalate stones. Compromised kidney function exacerbates the disease and results in oxalate accumulation and crystallization in bones, eyes, skin, and heart, leading to severe illness and death. Current treatment options are very limited and include frequent renal dialysis or combined organ transplantation of liver and kidney, a procedure with high morbidity that is limited due to organ availability. While some patients are fully responsive to vitamin B6 therapy, there are no approved pharmaceutical therapies for PH1.

Lumasiran is an experimental, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) that encodes glycolate oxidase (GO) in development for the treatment of PH1. By silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1.

Lumasiran has received U.S. and E.U. Orphan Drug designations, a Breakthrough Therapy designation and pediatric rare disease designation from the FDA, and a Priority Medicines (PRIME) designation from the European Medicines Agency. It is also under review by the EMA, which granted it an accelerated assessment, awarded to medicines deemed to be of major public health interest and therapeutic innovation, and is designed to bring new treatments to patients more quickly.

“Award of Priority Review status adds to the previous grants of Breakthrough Therapy and Pediatric Rare Disease Designations,” said Pritesh Gandhi, vice president and general manager of the lumasiran program at Alnylam. “Together, we believe these underscore the potential of lumasiran to address the underlying pathophysiology of PH1 and the urgent need for an FDA-approved treatment for this progressive, devastating disease where liver transplantation is currently the only treatment that addresses the root cause of disease.”

Photo: Pritesh Gandhi, vice president and general manager of the lumasiran program at Alnylam



Stay Connected

Sign up for updates straight to your inbox.