FDA Approves Nedosiran for Patients With Primary Hyperoxaluria Type 1

The FDA has approved nedosiran (Rivfloza; Novo Nordisk Inc) injection in 80 mg, 120 mg, and 160 mg strengths to lower urinary oxalate levels in children aged 9 years and older and adults with primary hyperoxaluria type 1 (PH1) with relatively preserved kidney function, according to a statement from Novo Nordisk.¹

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Nedosiran is a once-monthly subcutaneous ribonucleic acid interference (RNAi) therapy, designed to inhibit the expression of liver enzyme lactate dehydrogenases leading to oxalate overproduction in patients with PH1.¹

"RNA[i] is a proven treatment approach for individuals with PH1. With the approval of [nedosiran], we now have a novel treatment that lowers oxalate production safely and effectively," David S. Goldfarb, MD, clinical chief of the nephrology division at New York University (NYU) Langone Medical Center and professor of medicine and physiology at NYU Grossman School of Medicine, said in a statement. "Using the GalXC RNAi platform, [nedosiran] targets the liver-specific lactate dehydrogenase enzyme, which is the final step of oxalate production in PH1."¹

The approval was based on results from the phase 2 PHYOX2 clinical trial (NCT03847909) and data from the ongoing phase 3 PHYOX3 extension study (NCT04042402). In the PHYOX2 study, the data met the primary endpoint, demonstrating that those treated with nedosiran had a marked reduction from baseline in 24-hour urinary oxalate (Uox) excretion from day 90 to day 180. Investigators used the area under the curve (AUC) analysis to measure the percentage change from baseline in 24-hour Uox.¹

Furthermore, the least-squares mean between the group difference of AUC24-hour Uox was 4976, showing a significant difference between the drug group and the placebo group over 90 days, according to the statement. The most common adverse effects included injection site reaction, which was reported in 20% or more individuals of the study.¹

In the PHYOX3 study, the interim results showed that 13 patients with PH1 maintained a reduction in 24-hour Uox excretion after receiving an additional 6 months of treatment.¹

According to a review in Nature Reviews Urology, PH1 comes from a family of rare autosomal-recessive genetic disorders. The prevalence is approximately less than 3 in every 1,000,000 individuals, or as high as 1 in 58,000, according to the investigators.²

At the time of the study, nedosiran was not approved by the FDA. They stated that even though there have been new developments in therapeutics for PH1, there is still work that needs to be done. The study authors indicated that long-term safety and outcome data are still lacking, and there should be further work regarding when patients start developing resistance to the therapeutics.²

Novo Nordisk stated that nedosiran should be made available to patients as early as 2024.¹

Reference

1. FDA approves Rivfloza for children ≥9 years old and adults living with primary hyperoxaluria type 1 (PH1), a rare genetic condition. News release. Novo Nordisk. October 2, 2023. Accessed October 2, 2023. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=166325
2. Shee K, Stoller ML. Perspectives in primary hyperoxaluria - historical, current and future clinical interventions. Nat Rev Urol. 2022;19(3):137-146. doi:10.1038/s41585-021-00543-4