FDA approves Rivfloza™ for children ≥9 years old and adults living with primary hyperoxaluria type 1 (PH1), a rare genetic condition

PLAINSBORO, N.J., Oct. 2, 2023 /PRNewswire/ -- Novo Nordisk announced today that the U.S. Food and Drug Administration (FDA) has approved Rivfloza^TM (nedosiran) injection 80 mg, 128 mg, or 160 mg, a once-monthly subcutaneous ribonucleic acid interference (RNAi) therapy, 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.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.² PH1 is the most clinically prevalent (roughly ~80% of PH patients) and severe of the three subtypes of PH.³ PH1 is a progressive metabolic disorder that primarily affects the kidneys and can lead to progressive kidney damage.² In the U.S., it is estimated that over 2,000 people are living with PH1.⁴

"The FDA approval of Rivfloza^TM 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 PHYOX^TM2 clinical trial and interim data from the ongoing phase 3 PHYOX^TM3 extension study.¹ PHYOX^TM2 met its primary endpoint, showing that patients treated with Rivfloza^TM 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 AUC_{24-hour Uox} was 4976 (95% CI: 2803, 7149; p<0.0001), which was significant between the Rivfloza^TM 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 PHYOX^TM3 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 Rivfloza^TM.¹

"RNA interference is a proven treatment approach for individuals with PH1. With the approval of Rivfloza^TM, 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, Rivfloza^TM targets the liver-specific lactate dehydrogenase enzyme, which is the final step of oxalate production in PH1."

Reflecting on the approval of Rivfloza^TM 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 Rivfloza^TM 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."

Rivfloza^TM, the first RNAi therapeutic by Novo Nordisk, was developed using the proprietary GalXC^TM RNAi technology platform. Rivfloza^TM 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.

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

What is Rivfloza^TM?

Rivfloza^TM (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 Rivfloza^TM is safe and effective in children younger than 9 years of age.

Important Safety Information
What are the possible side effects of Rivfloza^TM? 
The most common side effects of Rivfloza^TM include injection site reactions, such as reddening, pain, bruising, rash, or dimple at the site of injection.

Please click here for Prescribing Information.

About the PHYOX™2 & PHYOX™3 studies
PHYOX^TM2 was a pivotal, randomized, double-blind trial comparing Rivfloza^TM and placebo in patients with primary hyperoxaluria (PH)1 or PH2 and an eGFR ≥30 mL/min/1.73 m².^5,6 Too few PH2 patients were enrolled to evaluate efficacy in the PH2 population, therefore, Rivfloza^TM is only indicated for patients with PH1.^5,6 In the PHYOX^TM2 study, 35 patients with PH1 or PH2 received either Rivfloza^TM (n=23) or placebo (n=12) once monthly for six months.^5,6 The primary endpoint of PHYOX^TM2 was the percent change from baseline in 24-hour urinary oxalate (Uox) excretion as measured by area under the curve (AUC) from Day 90 to Day 180.^5,6

The PHYOX^TM3 study is an ongoing long-term, multidose, open-label, extension trial designed to further evaluate the long-term safety and efficacy of monthly subcutaneous nedosiran in individuals who completed a previous PHYOX^TM trial.⁷

About primary hyperoxaluria type 1 (PH1)
Primary hyperoxaluria type 1 (PH1) is a subtype of primary hyperoxalurias (PH), a family of rare, autosomal recessive genetic disorders of hepatic glyoxylate metabolism. The three genetically different subtypes of PH (PH1, PH2, and PH3) each have a distinct enzyme deficiency that causes an abnormal increase in glyoxylate levels. Glyoxylate is converted to the metabolic end-product oxalate by hepatic lactate dehydrogenase (LDH). Oxalate is normally filtered by the kidneys, but in case of excessive levels as occurs in PH (hyperoxaluria) the oxalate will precipitate with calcium to form calcium oxalate crystals in the renal tubules and kidneys. This ultimately leads to the formation of kidney stones and/or nephrocalcinosis, and may lead to chronic kidney damage. Genetic studies suggest approximately 1 in 38,600 individuals are affected by PH worldwide, and researchers believe a large portion of cases go undiagnosed.² PH1 is the most clinically prevalent (roughly ~80% of PH patients) and severe of the three subtypes of PH.³

About Rivfloza^TM
Rivfloza^TM (nedosiran) injection, developed by Dicerna Pharmaceuticals, Inc., is a once-monthly subcutaneous ribonucleic acid interference (RNAi) therapy indicated 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, e.g., eGFR ≥30 mL/min/1.73 m².¹  Utilizing Novo Nordisk's proprietary GalXC^TM RNAi technology platform, Rivfloza^TM is designed to inhibit the expression of liver enzyme lactate dehydrogenase, that catalyzes the final common step in the glyoxylate metabolism pathway which leads to the oxalate overproduction in patients with PH1.

About Novo Nordisk 
Novo Nordisk is a leading global healthcare company that has been making innovative medicines to help people with diabetes lead longer, healthier lives for 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity and rare blood and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With U.S. headquarters in New Jersey and production and research facilities in seven states, Novo Nordisk employs nearly 6,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, and Twitter. 

References

1. Rivfloza^TM Prescribing Information Novo Nordisk Inc. September 2023
2. Hopp K, Cogal AG, Bergstralh EJ, et al. Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria. Journal of the American Society of Nephrology: JASN. 2015;26(10):2559-2570. doi:https://doi.org/10.1681/ASN.2014070698.
3. American Kidney Fund.org. Primary hyperoxaluria and oxalate: Symptoms, causes and treatment. kidneyfund.org. Accessed September 8, 2023. https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/primary-hyperoxaluria.
4. Novo Nordisk. Data on file.
5. Baum MA, Langman C, Cochat P, et al. PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2. Kidney International. 2023;103(1):207-217. doi:https://doi.org/10.1016/j.kint.2022.07.025.
6. ClinicalTrials.gov. A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (PHYOX2). Accessed Aug. 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03847909.
7. ClinicalTrials.gov. Long Term Extension Study in Patients with Primary Hyperoxaluria (PHYOX3). Accessed Aug. 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04042402.

Rivfloza^TM, PHYOX^TM, and GalXC^TM are registered trademarks of Novo Nordisk Health Care AG.
Novo Nordisk is a registered trademark of Novo Nordisk A/S.
© 2023 Novo Nordisk All rights reserved. US23NED00053 September 2023

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