FDA Grants Priority Review to Alnylam’s RNAi Therapy for Primary Hyperoxaluria Type 1

FDA

Alnylam Pharmaceuticals’ lumasiran for a chronic kidney stone disease was granted Priority Review status by the U.S. Food and Drug Administration (FDA). It will have a target action date of December 3, 2020.

Lumasiran is being developed as a treatment for primary hyperoxaluria type 1 (PH1). PH1 is an ultra-rare disease where excessive production of oxalate causes the deposit of calcium oxalate crystals in the kidneys and urinary tract. This can lead to recurrent kidney stones and nephrocalcinosis. It can also cause damage to the renal system, kidneys and urinary tract.

Lumasiran is an investigational, subcutaneously administered RNA interference (RNAi) therapeutic that targets hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO). By silencing HAO1 and depleting the GO enzyme, the drug inhibits production of oxalate.

The drug leverages the company’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology. This allows quarterly subcutaneous maintenance dosing with increased potency and durability. The drug has been designated an Orphan Drug in the U.S. and Europe, as well as a Breakthrough Therapy Designation and pediatric rare disease designation by the FDA and a Priority Medicines (PRIME) designation from the European Medicines Agency (EMA).

“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, vice president and general manager of the Lumasiran Program at Alnylam.

Gandhi added, “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.”

RNAi is a technique used to silence abnormal gene expression. The first ever drug approved using RNAi was Alnylam’s Onpattro (patisiran), which launched in August 2018 for polyneuropathy in hATTR amyloidosis. The second RNAi therapy approved was also an Alnylam product, Givlaari (givosiran) for acute hepatic porphyria (AHP).

Givlaari has a price tag of about $575,000 annually, with the average price after discounts running around $442,000 per year, with a vial of the drug running $39,000. That is similar to the price of Onpattro, which runs up to $450,000, with payers typically having worked out deals linking the cost to patient outcomes. There is also usually a prevalence-based adjustment, which means that if a payer finds higher-than-expected numbers of patients with the condition, Alnylam will pay the insurer a rebate.

Clarivate, a market analytics company, has added Patisiran to the top six list of blockbusters likely to launch this year. Patisiran is projected to have 2022 sales of $1.22 billion.

Alnylam has grown to 950 staffers with plans to add another 150 by the end of this year. Ten of those will be in Tokyo, and the company has plans to build out Latin America and other countries.

On December 17, 2019, Alnylam presented topline data from the ILLUMINATE-A Phase III clinical trial of lumasiran for PH1. It met its primary efficacy endpoint and all tested secondary endpoints. The primary efficacy endpoint was percent change from baseline, relative to placebo, in 24-hour urinary oxalate excretion averaged across months 3 to 6. The drug showed what the company called an “encouraging safety and tolerability profile.”

At the time, Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation, said, “The ILLUMINATE-A results represents a significant landmark for the PH1 patient community. These patients live with the angst of not knowing when the next kidney stone will come or for how long their kidneys will keep working, and they grapple with the possibility of needing new organs. We have lived with the hope that someday patients living with PH1 and their families would finally have a treatment with the potential to have a positive impact on their health and alleviate some of that angst.”

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