Nedosiran

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.

• RIVFLOZA is indicated to lower urinary oxalate levels in children 2 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 m 2 [see Clinical Pharmacology (‎ 12.3 )], Clinical Studies (‎ 14.1 )]. RIVFLOZA is an LDHA -directed small interfering RNA indicated to lower urinary oxalate levels in children 2 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 m 2 .

• None. None.contraindicated

The recommended dosage is shown below and is administered subcutaneously once monthly. (‎ 2.1 ) Body weight Less than 39 kg 39 kg to less than 50 kg 50 kg and above Age 2 to less than 12 years 3.3 mg/kg 128 mg 160 mg Age 12 years and older 128 mg 160 mg See full Prescribing Information for important administration instructions. (‎ 2.2 ) 2.1 Recommended Dosage RIVFLOZA is administered subcutaneously once monthly at the recommended doses shown in Table 1 . Dosing is based on actual body weight. Table 1: RIVFLOZA Dose Regimen in Adults and Pediatric Patients (2 years of age and older) Body weight Less than 39 kg 39 kg to less than 50 kg 50 kg and above Age 2 to less than 12 years 3.3 mg/kg 128 mg 160 mg Age 12 years and older 128 mg 160 mg 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. 2.2 Administration Instructions Pre-filled syringe: A healthcare provider, caregiver, or patient 12 years of age and older may inject RIVFLOZA using the pre-filled syringe. In pediatric patients 2 to less than 12 years of age who weigh ≥39 kg, a healthcare provider or caregiver may inject RIVFLOZA using the pre-filled syringe. Vials: RIVFLOZA vials are intended for use under the guidance and supervision of a healthcare provider.

Most common adverse reactions (reported in ≥20% of patients) are injection site reactions. (‎ 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-844-906-5099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of RIVFLOZA has been evaluated in one placebo-controlled clinical trial (PHYOX2) and one open-label extension study (PHYOX3). Across these studies, 29 adults and 12 children with PH1 have been treated with RIVFLOZA. Patients with PH1 in these studies ranged in age from 9 to 46 years at first dose. The median duration of exposure was approximately 15 months (range 1-29 months). Overall, 38 patients with PH1 were treated for at least 6 months, 24 patients for at least 12 months, and 16 patients for at least 18 months. In the randomized, placebo-controlled, double-blind PHYOX2 trial in pediatric and adult patients 9 to 46 years of age, 18 patients with PH1 received RIVFLOZA and 11 patients received placebo. Of the 18 patients treated with RIVFLOZA, 17 patients received ≥5 months of active treatment. The most common adverse reactions were injection site reactions, which were reported in 7 patients with PH1 (39%) on RIVFLOZA as compared to no patients on placebo.

8.1 Pregnancy Risk Summary Available data from reports of pregnancy in clinical trials with RIVFLOZA are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed when nedosiran was administered to pregnant mice at doses up to approximately 58 times the maximum recommended human dose (MRHD) of 160 mg nedosiran (equivalent to 170 mg nedosiran sodium) per dose, based on body surface area (BSA) or upon administration of a mouse-specific (pharmacologically active) analog. Subcutaneous administration of nedosiran to pregnant rabbits during the period of organogenesis at doses approximating the MRHD resulted in increased fetal loss in the presence of maternal toxicity. Adverse developmental outcomes (fetal cardiovascular and skeletal malformations) were observed at a dose approximately 2 times the MRHD (see Data). Nedosiran is not pharmacologically active in rabbits or mice. The cause for the embryo-fetal toxicities observed in rabbits remains unclear. The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

Metabolism

The pharmacokinetic (PK) properties of RIVFLOZA were evaluated following administration of single and multiple dosages in patients with PH1 or PH2 as summarized in Table 2 . Table 2: Pharmacokinetic Parameters of Nedosiran Nedosiran General Information Steady State Exposure C max [Mean (%CV)] 844 (44) ng/mL AUC 0-last [Mean (%CV)] 13600 (36) ng * h/mL Dose Proportionality Nedosiran exhibited a dose-proportional increase in plasma exposure following single subcutaneous doses from 1.5 to 6.0 mg/kg.

• Sep 29, 2023NDANDA215842Novo

1. 1Urine Oxalate Increased325%
2. 2Inappropriate Schedule Of Product Administration217%
3. 3Rash217%
4. 4Abdominal Pain18.3%
5. 5Amenorrhoea18.3%
6. 6Bone Pain18.3%
7. 7Death18.3%
8. 8Dehydration18.3%
9. 9Diabetes Mellitus18.3%
10. 10Drug Ineffective18.3%
11. 11Febrile Infection18.3%
12. 12Haemoglobin Increased18.3%
13. 13Hyperoxalaemia18.3%
14. 14Hyperoxaluria18.3%
15. 15Influenza18.3%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Nedosiran as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function
  Completed · Phase 2 · Interventional · 27 enrolled · Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
  NCT05001269updated 2026-04-16
• Safety & Efficacy of DCR-PHXC in Patients With PH1 and ESRD
  Recruiting · Phase 2 · Interventional · 28 enrolled · Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
  NCT04580420updated 2025-12-24
• Treatment of Primary Hyperoxaluria Type 1 With Nedosiran
  No longer available · Expanded access · Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
  NCT05993416updated 2025-07-22
• Long Term Extension Study in Patients With Primary Hyperoxaluria
  Active not recruiting · Phase 3 · Interventional · 75 enrolled · Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
  NCT04042402updated 2025-05-30
• Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients
  Completed · Phase 1 · Interventional · 6 enrolled · Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
  NCT04555486updated 2024-09-19
• A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2
  Completed · Phase 2 · Interventional · 35 enrolled · Novo Nordisk A/S
  NCT03847909updated 2024-05-22

Frequently asked questions

How does Nedosiran work?

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.

What is Nedosiran used for?

According to FDA labeling, Nedosiran carries indications including: RIVFLOZA is indicated to lower urinary oxalate levels in children 2 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 m 2 [see Clinical Pharmacology (‎ 12.3 )], Clinical Studies (‎ 14.1 )]. RIVFLOZA is an LDHA -directed small interfering RNA indicated to lower urinary oxalate levels in children 2 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 m 2 .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nedosiran?

Nedosiran is classified as Various alimentary tract and metabolism products.

What are the brand names for Nedosiran?

Nedosiran is marketed under brand names including Rivfloza.

What are the contraindications for Nedosiran?

Nedosiran labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.