FDA ALERT

FDA Approves Nedosiran for Patients 9 Years of Age and Older With Primary Hyperoxaluria Type 1

Anthony Calabro, MA

In late September 2023, the FDA approved nedosiran, a once-monthly RNA interference medication administered subcutaneously to lower urinary oxalate levels in patients aged 9 years and older with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function.1 Nedosiran is expected to be available for prescription in early 2024, according to a press release.2

Primary hyperoxaluria is a rare group of genetic metabolic disorders that cause overproduction of oxalate by the liver. There are three PH subtypes, of which PH1 is the most common and most severe, accounting for about 80% of all patients.

The once-monthly, RNA interference injection medication received FDA approval based on results from two studies: the phase II PHYOX2 clinical trial and phase III PHYOX3 extension study. The clinical trial evaluated the efficacy and safety of nedosiran in patients 6 years of age and older with PH1 or PH2 and an eGFR of at least 30 mL/min/1.73m2.1

Study participants were randomly assigned to receive either nedosiran (n = 23) or placebo (n = 12) subcutaneously once monthly. The median age was 20 years (range: 9-46 years of age), 51% were female, 83% had PH1, and 17% had PH2. Too few patients with PH2 were enrolled in the study to evaluate safety and efficacy. The primary endpoint was the percent change from baseline for reduction in 24-hour urinary oxalate excretion, based on the area under the curve (AUC) from Days 90 to 180 (AUC24-hour Uox).1

The study results showed that the least-squares mean AUC24-hour Uox was -3486 (95% CI, -5025, to -1947) in the nedosiran group compared with 1490 (95% CI, 781-3761) in the placebo group. The statistically significant between group difference was 4976 (95% CI, 2803-7149; p < 0.0001).1

Patients were eligible to enroll in an ongoing phase 3, single-arm extension study after 6 months of treatment in the phase 2 trial. The 13 patients with PH1 who received an additional 6 months of treatment maintained the reduction in urinary oxalate.1

Injection site reactions was the most common adverse reaction for nedosiran, which was reported in seven patients compared with no patients in the placebo group. The FDA approved injection medication for three dosages depending on patient weight: 80 mg, 128 mg, and 160 mg.1

 

References:

  1. Rivfloza. Highlights of prescribing information. US Food and Drug Administration. Accessed January 4, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215842s000lbl.pdf.
  2. FDA approves Rivfloza™ for children ≥9 years old and adults living with primary hyperoxaluria type 1 (PH1), a rare genetic condition. Press release. Novo Nordisk US; October 2, 2023. Accessed January 4, 2024. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=166325.