Date: 29-May-2020

US FDA Accepts Alnylams NDA For Lumasiran And Grants Priority Review Status For Primary Hyperoxaluria Type 1

Alnylam Pharmaceuticals, a leading RNAi therapeutics company, announced that the US Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for lumasiran, an investigational RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – in development for the treatment of primary hyperoxaluria type 1 (PH1). The FDA also granted Priority Review for the NDA, a designation for medicines that have the potential to provide significant improvements in the treatment, prevention or diagnosis of a serious disease, with the goal of FDA taking action within six months compared to 10 months under standard review.


“We are pleased to have received Priority Review status for lumasiran and look forward to continuing to work closely with the FDA during the review process,” said Pritesh J. Gandhi, PharmD., vice president and general manager, Lumasiran Program at Alnylam. “Award of Priority Review status adds to the previous grants of Breakthrough Therapy and Pediatric Rare Disease Designations. 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.”


The FDA has set an action date of December 3, 2020 under the Prescription Drug User Fee Act (PDUFA), and the Agency has indicated that they are not currently planning an advisory committee meeting as part of the NDA review.


In addition, the Marketing Authorisation Application (MAA) for lumasiran has been submitted to and validated by the European Medicines Agency (EMA). Lumasiran was previously granted an accelerated assessment by the EMA, which is 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. Accelerated assessment potentially reduces the Agency’s evaluation time from 210 to 150 days.


Lumasiran has also previously received Orphan Drug Designations for the treatment of PH1 in the US and Europe and has received a Priority Medicines (PRIME) designation from the EMA.


Lumasiran is an investigational, subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) in development for the treatment of primary hyperoxaluria type 1 (PH1). HAO1 encodes glycolate oxidase (GO).Thus, by silencing HAO1 and depleting the GO enzyme, lumasiran inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. Lumasiran utilizes Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables quarterly subcutaneous maintainence dosing with increased potency and durability and a wide therapeutic index. Lumasiran has received both US and EU Orphan Drug Designations, a Breakthrough Therapy Designation and pediatric rare disease designation from the US Food and Drug Administration (FDA), and a Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). The safety and efficacy of lumasiran are being evaluated by the FDA and EMA.


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 and 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 as the excess oxalate can no longer be effectively excreted, resulting in subsequent 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. Although a minority of patients are fully responsive to vitamin B6 therapy, there are no approved pharmaceutical therapies for PH1