General Information

Rivfloza (nedosiran) is an LDHA-directed small interfering RNA.

Rivfloza is 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.

Rivfloza is an injection subcutaneously administered once monthly at the recommended doses below. Dosing is based on actual body weight.

Age

Body Weight

Dosing Regimen

Adults and adolescents 12 years and older

Greater than or equal to 50 kg:
Less than 50 kg:

160 mg once monthly (Pre-filled Syringe, 1 mL)
128 mg once monthly (Pre-filled Syringe, 0.8 mL)

Children 9 to 11 years

Greater than or equal to 50 kg:
Less than 50 kg:

160 mg once monthly (Pre-filled Syringe, 1 mL)
3.3 mg/kg once monthly, not to exceed 128 mg (Vial, dose volume rounded to nearest 0.1 mL)

Missed Dose:

If a planned dose is missed, administer Rivfloza as soon as possible. If the planned dose is missed by more than 7 days, administer Rivfloza as soon as possible and resume monthly dosing from the most recently administered dose.

Mechanism of Action

Rivfloza (nedosiran) is a double-stranded siRNA, conjugated to GalNAc aminosugar residues. After subcutaneous administration, the GalNAc-conjugated sugars bind to asialoglycoprotein receptors (ASGPR) to deliver nedosiran to hepatocytes. Nedosiran reduces levels of hepatic lactate dehydrogenase (LDH) via the degradation of LDHA messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. The reduction of hepatic LDH by nedosiran reduces the production of oxalate by the liver, thereby reducing subsequent oxalate burden.

Clinical Trial Results

FDA approval of Rivfloza was based on results of the pivotal phase 2 PHYOX2 clinical trial and interim data from the ongoing phase 3 PHYOX3 extension study.

PHYOX2 met its primary endpoint, showing that patients treated with Rivfloza achieved a marked reduction from baseline in 24 hour-urinary oxalate (Uox) excretion from Day 90 to Day 180. 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, which was significant between the Rivfloza and placebo groups over the 90 days. Interim results from the PHYOX3 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.