Rivfloza (nedosiran) / Alnylam, Novo Nordisk - LARVOL DELTA

PHYOX8: Nedosiran in Pediatric Patients with Primary Hyperoxaluria (KIDNEY WEEK 2025) - P2 | "Conclusion Nedosiran was well-tolerated in children aged from 10 months to 11 years with PH1. Nedosiran treatment resulted in a notable reduction of mean Uox:Cr in this population."

Clinical • Late-breaking abstract • Genetic Disorders • Metabolic Disorders • Musculoskeletal Pain • Nephrology • Pediatrics • Renal Calculi • LDHA

Evaluating Physician Preferences for siRNA Therapy in Patients with Primary Hyperoxaluria Type 1 (KIDNEY WEEK 2025) - "The small interfering RNA (siRNA) therapies lumasiran and nedosiran are effective treatment options. Conclusion Physicians prioritized patient-related factors and regimen complexity when selecting a PH1 treatment. They preferred an siRNA treatment that was easy to use, required minimal HCP involvement/allowed for self-administration and did not negatively impact the patient's daily activities, including school or work."

Clinical • Hepatology • Nephrology

PEDIATRIC PRIMARY HYPEROXALURIA TYPE 1: A CLINICAL REVIEW OF CONVENTIONAL AND EMERGING THERAPIES (ESPN 2025) - "While 2 patients had rising oxalate levels after 2 years of treatment, one was switched to nedosiran with slight improvement...Two patients treated with lumasiran showed improved nephrocalcinosis, while the patient on conventional treatment also showed improved ultrasound lesions... PH1 has a variable prognosis, emphasizing the importance of early diagnosis. This condition should be suspected after lithiasis events or nephrocalcinosis. Conventional treatment is essential for reducing oxalate levels, but often insufficient."

Clinical • Review • Acute Kidney Injury • Chronic Kidney Disease • Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease

RNA interference medication and transplantation procedures in patients with primary hyperoxaluria type 1 (PH1). (PubMed, Nephrol Dial Transplant) - "Pox should not be the sole parameter to decide on Tx procedure. In patients with minor oxalate deposition, no SOG deterioration and sensitivity to vitamin B6 or under efficacious RNAi treatment, iKTx can be considered. Severe (and deteriorating) systemic oxalosis, high Pox during RNAi treatment and maximum dialysis, makes us reconsider combined or sequential LKTx rather than iKTx. Patients with severe systemic oxalosis at time of diagnosis still have a high mortality rate."

Journal • Nephrology • Renal Disease • Transplantation

Primary hyperoxaluria type 1 - an unexpected diagnosis after kidney transplantation. (PubMed, Kidney Blood Press Res) - "Currently, we have access to novel RNA interference (RNAi) therapeutics such as lumasiran and nedosiran, which reduce hepatic oxalate production, however, they are prohibitively expensive in most countries. This case highlights the importance of early diagnosis, which allows optimal supportive and/or RNAi therapy and appropriate qualification for kidney transplantation in cases of end-stage kidney disease. This is particularly important as isolated kidney transplantation (without concomitant liver transplantation) can lead to rapid loss of graft function and may ultimately prove futile."

Journal • Chronic Kidney Disease • Inflammation • Metabolic Disorders • Nephrology • Renal Calculi • Transplantation

Updates on Pharmacological Therapy for Urolithiasis (UAA 2025) - "In primary hyperoxaluria (PH), novel RNA interference (RNAi) agents like lumasiran and nedosiran significantly lower urinary oxalate levels, offering promising alternatives for patients unresponsive to pyridoxine...Xanthine oxidase inhibitors (allopurinol, febuxostat) are reserved for hyperuricemic patients...Medical expulsive therapy (MET) with alpha-blockers (tamsulosin) remains effective for distal ureteral stones (5–10 mm), reducing time to expulsion and need for surgery...Operative times vary, with suction PCNL often being faster for large stones (47–82 min) but requiring fluoroscopy, while suction RIRS avoids tract-related risks but may necessitate staged procedures for stones >2 cm. Cost-effectiveness analyses favor suction PCNL due to fewer retreatments, though RIRS reduces radiation exposure."

Infectious Disease • Nephrology • Renal Calculi • Urolithiasis

Suction PCNL vs Suction RIRS? Do We Have a Winner (UAA 2025) - "In primary hyperoxaluria (PH), novel RNA interference (RNAi) agents like lumasiran and nedosiran significantly lower urinary oxalate levels, offering promising alternatives for patients unresponsive to pyridoxine...Xanthine oxidase inhibitors (allopurinol, febuxostat) are reserved for hyperuricemic patients...Medical expulsive therapy (MET) with alpha-blockers (tamsulosin) remains effective for distal ureteral stones (5–10 mm), reducing time to expulsion and need for surgery...Operative times vary, with suction PCNL often being faster for large stones (47–82 min) but requiring fluoroscopy, while suction RIRS avoids tract-related risks but may necessitate staged procedures for stones >2 cm. Cost-effectiveness analyses favor suction PCNL due to fewer retreatments, though RIRS reduces radiation exposure."

Infectious Disease • Nephrology • Renal Calculi • Urolithiasis

PHYOX3: Nedosiran Long-Term Safety and Efficacy in Patients With Primary Hyperoxaluria Type 1. (PubMed, Kidney Int Rep) - P1, P2, P3 | "Four participants discontinued treatments (1 pregnancy and 3 withdrawals), and no deaths were reported. Nedosiran was well-tolerated, reduced average Uox levels, reduced kidney stone occurrence, and maintained stable renal function for over 3 years."

Journal • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1. (PubMed, Clin Pharmacokinet) - P1, P2, P3 | "Simulations based on the final Pop-PK/PD model support the 3.5 mg/kg Q1M dosing regimen in children aged 2 to < 12 years with PH1 and relatively intact kidney function (eGFR ≥30 mL/min/1.73 m2)."

Journal • PK/PD data • Nephrology • Pediatrics • Renal Disease

PHYOX 3: Long Term Extension Study in Patients With Primary Hyperoxaluria (clinicaltrials.gov) - P3 | N=75 | Active, not recruiting | Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Nephrology • Renal Disease

PHYOX8: Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function (clinicaltrials.gov) - P2 | N=25 | Completed | Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company | Recruiting ➔ Completed

Trial completion • Nephrology • Pediatrics

Treatment preferences among individuals with primary hyperoxaluria type 1 (PH1): a real-world study. (PubMed, Orphanet J Rare Dis) - "This study shows that patients with PH1 value treatments that are convenient and fit their lifestyle."

Journal • Real-world evidence • Genetic Disorders • Nephrology

The efficacy and safety of RNA interference for the treatment of primary hyperoxaluria: a systematic review and meta-analysis. (PubMed, Clin Kidney J) - "Furthermore, high-dose and long time-duration RNAi therapy may have a better clinical effect, and acceptable safety. The efficacy of RNAi combined with hemodialysis seems to be promising in PH treatment."

Journal • Retrospective data • Review • Genetic Disorders • Hepatology • Nephrology • Renal Disease

A Targeted Release Capsule of Lanthanum Carbonate: a New Efficient Cheap Treatment for Primary Hyperoxalurias. (PubMed, Kidney Int Rep) - "Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate synthesis. is a promising repurposed, efficient, nontoxic, and cheap drug, lacking serious side effects in the treatment of any type of PH in whatever place in the world. A randomized controlled trial supporting this proof-of-concept is the next step."

Journal • Gastrointestinal Disorder • Nephrology • Renal Disease

Concomitant Treatment With Lumasiran and Nedosiran in a Child With Primary Hyperoxaluria Type 1. (PubMed, Kidney Int Rep) - No abstract available

Journal • Nephrology

Global access to management of primary hyperoxaluria: a survey on behalf of OxalEurope, G&K working group of the ERA, and ESPN. (PubMed, Nephrol Dial Transplant) - "We found global disparities in access to optimal management of PH patients, disproportionately affecting low-income countries, but even existing between high-income countries. These results may provide support for initiatives to improve the outcome of PH patients worldwide in an era of new targeted therapeutic treatments."

Journal • Hepatology • Nephrology • Rare Diseases • Transplantation

Is RNA interference therapy sufficient to avoid liver transplantation in severe infantile Primary Hyperoxaluria type 1? (IPNA 2025) - "In such cases, dual therapy with lumasiran and nedosiran might temporarily be considered, though being very expensive. Alternatively, combined or sequential liver transplantation remains unavoidable."

Genetic Disorders • Hepatology • Metabolic Disorders • Nephrology • Renal Disease • Transplantation

Isolated kidney transplantation in an adolescent on Lumasiran therapy for Primary Hyperoxaluria type 1 (IPNA 2025) - "Aims/Purpose Primary hyperoxaluria type 1 (PH1) is a rare inherited disorder of glyoxylate metabolism resulting in overproduction and deposition of oxalate in end-organs, lead ing to kidney failure and systemic oxalosis. We provide and discuss details of peri-transplant management to reduce POx with pre-emptive dialysis. We highlight the importance of confirming long-term access to siRNA therapy and discuss contingency plans ahead of transplant, including additional strategies such as the use of Nedosiran, Stiripentol and Tolvaptan."

Genetic Disorders • Nephrology • Transplantation

Compassionate use of nedosiran in paediatric patients with Primary Hyperoxaluria Type 1: A case study from Nelson Mandela Children's Hospital, South Africa (IPNA 2025) - "Of importance, the nedosiran therapy was associated with an improved quality of life.To the best of our knowledge, this is the first report on the use of nedosiran in Africa for the treatment of PH1. It highlights the drug's safety and efficacy and its potential benefit in improving the quality of life for patients enduring the complications of untreated PH1.Further research is needed to elucidate the full therapeutic potential and safety profile of nedosiran in paediatric patients with PH1 and to estimate the cost-utility of using the drug in resource-limited settings."

Case study • Clinical • Anemia • Hematological Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Orthopedics • Pain • Pediatrics

Development, opportunities, and challenges of siRNA nucleic acid drugs. (PubMed, Mol Ther Nucleic Acids) - "The US Food and Drug Administration has approved six siRNA drugs in recent years: patisiran, givosiran, lumasiran, vutrisiran, inclisiran, and nedosiran. This review summarizes the history of siRNA drug development and the mechanisms of action, with a focus on the drug targets, indications, and key clinical trial results to introduce the status of both marketed drugs and those currently in clinical trials. Additionally, this review provides a brief analysis of several key stages of the commercialization process of siRNA drugs."

Journal • Review

Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8). (PubMed, Pediatr Nephrol) - P2 | "Nedosiran was well tolerated, with only 3 participants experiencing at least one serious adverse event, none considered treatment-related. The incidence of injection site reactions was 6.7% (1/15 participants). In conclusion, nedosiran treatment led to a significant and sustained reduction of Uox levels in children with PH1. These findings support nedosiran treatment in pediatric patients to reduce Uox and shows promise for limiting PH1-related complications."

Journal • P2 data • Chronic Kidney Disease • Nephrology • Pediatrics • Renal Calculi • Renal Disease • Urology

Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures. (PubMed, Noncoding RNA) - "In this study, we compared the utilities of three advanced computational tools, namely RNAComposer, Rosetta FARFAR2, and the latest AlphaFold 3, to predict the 3D structures of various forms of RNAs, including the small interfering RNA drug, nedosiran, and the novel bioengineered RNA (BioRNA) molecule showing therapeutic potential...However, there were significant discrepancies among three computational tools in predicting the distal loop of human pre-microRNA and larger BioRNA (tRNA fused pre-miRNA) molecules whose 3D structures have not been characterized experimentally. While computational predictions show considerable promise, their notable strengths and limitations emphasize the needs for experimental validation of predictions besides characterization of more RNA 3D structures."

Journal

Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria. (PubMed, J Inherit Metab Dis) - "In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi-based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3."

Journal • Review • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Transplantation • Urolithiasis

PHYOX7: Safety & Efficacy of DCR-PHXC in Patients With PH1 and ESRD (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company | N=17 ➔ 28 | Trial completion date: May 2025 ➔ Jan 2032 | Trial primary completion date: Nov 2024 ➔ Dec 2031

Enrollment change • Trial completion date • Trial primary completion date • Chronic Kidney Disease • Nephrology • Renal Disease

Evaluating Efficacy and Safety of RNA Therapies Lumasiran and Nedosiran in Patients With Primary Hyperoxaluria Type 1: A Systematic Literature Review (ISPOR-EU 2024) - P1/2 | "This SLR demonstrates that lumasiran and nedosiran are effective in lowering UOx levels, improving renal outcomes with favorable safety profiles, thus emphasizing their potential as long-term therapies for PH1."

Clinical • Review • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi