Drug updated on 4/16/2024
| Dosage Form | Injection (subcutaneous; 80 mg [0.5 mL] single-dose vials, 128 mg [0.8 mL] single-dose pre-filled syringes, 160 mg [1 mL] single-dose pre-filled syringes) |
| Drug Class | LDHA-directed small interfering RNAs |
| Ongoing and Completed Studies | ClinicalTrials.gov |
Indication
- Indicated for lowering 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 square meters.
Summary
- Nedosiran (Rivfloza) is an N-acetyl-D-galactosamine-conjugated RNA interference agent that targets the hepatic lactate dehydrogenase enzyme, which mediates the final step of oxalate production in all genetic subtypes of primary hyperoxaluria. It is indicated for lowering urinary oxalate levels in children 9 years and older and adults with primary hyperoxaluria type 1 who have relatively preserved kidney function.
- The information was derived from three randomized controlled studies focusing on Nedosiran's safety, effectiveness, and considerations for different population subgroups.
- In terms of safety, Nedosiran demonstrated a well-tolerated profile with few side effects, mainly including mild injection-site reactions. No significant safety concerns were identified, suggesting it has a competitive safety profile compared to other options.
- As for its effectiveness, Nedosiran actively lowered 24-hour urinary oxalate excretion across different population subgroups. A higher proportion of treated participants achieved normal or near-normal excretion compared to placebo, especially evident in PH1 patients, but not consistent in PH2 patients.
- Although direct comparisons with other drugs are not provided; however, based on its unique mechanism through RNA interference targeting hepatic lactase dehydrogenase presents a novel approach, potentially offering advantages over existing treatments particularly for PH1 patients where it effectively reduces oxalic acid production—a key pathophysiological mechanism in primary hyperoxaluria.
- Regarding population types and subgroup considerations, Nedosiran’s efficacy varies across different genetic subtypes of Primary Hyperoxaluria (PH), showing the most benefit observed among those diagnosed with subtype one (PH1). This drug was studied across various doses among populations such as children aged nine years or above along with adults possessing relatively preserved kidney functions, indicating broad potential application possibilities, while optimal dosing suggests a fixed monthly dose could provide the best balance between efficacy and urinary oxalate response stability.
Product Monograph / Prescribing Information
| Document Title | Year | Source |
|---|---|---|
| Rivfloza (nedosiran) Prescribing Information. | 2023 | Novo Nordisk Inc., Plainsboro, NJ |
Randomized Controlled Trials
| Document Title | Sex Distribution | Year | Source |
|---|---|---|---|
| Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4) | 6Subjects F: 33% M: 67% | 2023 | Urolithiasis |
| PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2. | 35Subjects F: 51% M: 49% | 2023 | Kidney International |
| Safety, pharmacodynamics, and exposure-response modeling results from a first-in-human phase 1 study of nedosiran (PHYOX1) in primary hyperoxaluria | 18Subjects F: 50% M: 50% | 2021 | Kidney International |
Document Title
Sex Distribution:
F:33%
M:67%
6Subjects
Year:
2023
Source:Urolithiasis
Sex Distribution:
F:51%
M:49%
35Subjects
Year:
2023
Source:Kidney International
Sex Distribution:
F:50%
M:50%
18Subjects
Year:
2021
Source:Kidney International
Clinical Practice Guidelines
| Document Title | Year | Source |
|---|---|---|
| Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope. | 2023 | Nature Reviews Nephrology |