FDA approve Nedosiran Injection for rare kidney disorder

The US Food and Drug Administration has approved Nedosiran (Rivfloza), a once-monthly RNA interference (RNAi) injection for certain patients with primary hyperoxaluria type 1 (PH1).

The approval is for children 9 years and older and adult patients with primary hyperoxaluria type 1 (PH1having  relatively preserved kidney function.1

Primary hyperoxaluria (PH) is a rare genetic disease that causes overproduction of oxalate by the liver that is estimated to affect 1 in 38,600 individuals worldwide. PH1 is the most clinically prevalent (roughly ~80% of PH patients) and severe of the three subtypes of PH. PH1 is a progressive metabolic disorder that primarily affects the kidneys and can lead to progressive kidney damage. In the U.S., it is estimated that over 2,000 people are living with PH1.

"The FDA approval of RivflozaTM builds on Novo Nordisk's legacy of advancing research, fostering innovation and creating strategic partnerships to expand treatment options in rare diseases," said Blandine Lacroix, Senior Vice President, Strategy and Rare Disease at Novo Nordisk Inc. "We are committed to driving change on behalf of people living with rare diseases and helping address the significant unmet needs of the PH1 community. We look forward to making our first RNAi treatment available to people living with PH1 and the healthcare professionals partnering on their care."

This approval is based on the results of the pivotal phase 2 PHYOXTM2 clinical trial and interim data from the ongoing phase 3 PHYOXTM3 extension study.1 PHYOXTM2 met its primary endpoint, showing that patients treated with RivflozaTM achieved a marked reduction from baseline in 24 hour-urinary oxalate (Uox) excretion from Day 90 to Day 180.1,5 The percent change from baseline in 24-hour Uox was measured using an area under the curve (AUC) analysis. The least-squares (LS) mean between group difference of AUC24-hour Uox was 4976 (95% CI: 2803, 7149; p<0.0001), which was significant between the RivflozaTM and placebo groups over the 90 days.1 The most common adverse reaction (reported in ≥20% of patients) is injection site reactions.1 Interim results from the PHYOXTM3 extension study showed reductions in 24-hour Uox excretion were maintained in the 13 patients with PH1 who had received an additional six months of treatment with RivflozaTM.1

"RNA interference is a proven treatment approach for individuals with PH1. With the approval of RivflozaTM, we now have a novel treatment that lowers oxalate production safely and effectively," said Dr. David S. Goldfarb, MD Clinical Chief, Nephrology division, NYU Langone Medical Center and Professor of Medicine and Physiology, NYU Grossman School of Medicine. "Using the GalXC™ RNAi platform, RivflozaTM targets the liver-specific lactate dehydrogenase enzyme, which is the final step of oxalate production in PH1."

Reflecting on the approval of RivflozaTM and its potential impact, Kim Hollander, Executive Director, Oxalosis & Hyperoxaluria Foundation, said, "We appreciate Novo Nordisk's commitment to rare disease and welcome the addition of RivflozaTM as a new treatment option that provides those 9 and older living with PH1 and their loved ones with more choices when working with their healthcare professional to select what treatment pathway is best for them."

RivflozaTM, the first RNAi therapeutic by Novo Nordisk, was developed using the proprietary GalXCTM RNAi technology platform. RivflozaTM is designed to inhibit the expression of liver enzyme lactate dehydrogenase, a liver enzyme that catalyzes the final common step in the glyoxylate metabolism pathway which leads to the oxalate overproduction in patients with PH1.

RivflozaTM was developed by Dicerna Pharmaceuticals, Inc. which was acquired by Novo Nordisk in 2021. Novo Nordisk plans to make RivflozaTM available for eligible patients in early 2024.

What is RivflozaTM?

RivflozaTM (nedosiran) injection 80 mg, 128 mg, or 160 mg is a prescription medicine used to lower urinary oxalate levels in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function.

It is not known if RivflozaTM is safe and effective in children younger than 9 years of age.