Oxlumo (lumasiran) / Alnylam, Royalty, Novo Nordisk - LARVOL DELTA

A Case of Successful Kidney Transplant-Alone in Primary Hyperoxaluria Type 1 Using Lumasiran. (PubMed, Clin Transplant) - "At 12 months post-transplant, renal function remained stable (creatinine 0.82 mg/dL, serum oxalate <1.5 µmol/L). This case highlights RNAi therapy as a promising strategy to facilitate KTA in patients with PH1 and ESRD, potentially reducing the need for SLKT and its associated morbidity."

Journal • Chronic Kidney Disease • Nephrology • Transplantation

The oxalobiome: unraveling the role of gut microbiota in oxalate metabolism and its implications for kidney health and disease management. (PubMed, Clin Chim Acta) - "Innovative strategies, including RNA interference therapies (e.g., lumasiran, nedosiran), engineered probiotics, and gene-editing technologies, show promise in managing conditions like primary hyperoxaluria. Future studies should focus on mechanistic insights, standardized methodologies, and targeted microbiome-based therapies to optimize management strategies for hyperoxaluria and related systemic diseases. A comprehensive understanding of the oxalobiome is essential for developing precision medicine approaches that effectively address oxalate dysregulation and improve patient outcomes."

Journal • Review • Nephrology • Renal Calculi

The Dawn of Precision Medicine in Pediatric Nephrology: Lumasiran and the Era of siRNA Therapies for Primary Hyperoxaluria Type 1. (PubMed, J Pers Med) - "A paradigm shift in pediatric nephrology is signaled by Lumasiran, which changes the therapeutic approach from supportive care to precision, targeted medicine. Further research and empirical data will clarify its long-term advantages, the best ways to treat it, and the possible use of siRNA technologies for other genetic renal disorders."

Journal • Review • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease • Transplantation

Primary hyperoxaluria(s): from trials to real-life data and pipeline therapies. (PubMed, Kidney Int) - "Lumasiran, approved for PH1, inhibits glycolate oxidase and has demonstrated sustained reductions in urinary oxalate, stabilization of renal function, and reduced nephrocalcinosis in pivotal trials and in most patients in real-life. Nedosiran, targeting lactate dehydrogenase A, shows promise for PH1...Additionally, ensuring equitable access to expensive therapies presents a worldwide healthcare challenge. This mini-review summarizes recent milestones in PH pathophysiology, diagnostics, and therapeutics, emphasizing the transformative impact of RNAi therapies and future directions in managing this ultra-rare but devastating kidney disease."

Journal • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Transplantation • LDHA

Hyperoxaluria by the AGXT gene: a case report. (PubMed, J Med Case Rep) - "Primary hyperoxaluria type 1 remains a diagnostic and therapeutic challenge, particularly in resource-limited settings. Identification of specific AGXT variants offers key prognostic and therapeutic insights. Early genetic testing in children with unexplained nephrocalcinosis or recurrent nephrolithiasis may be cost-effective, enabling timely diagnosis, targeted treatment, and family screening while reducing the long-term burden and healthcare costs associated with end-stage renal disease."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Infectious Disease • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Transplantation • Urolithiasis

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Class-Specific Adverse Events of Patients Treated with Small Interfering RNA Therapeutics: A Disproportionality Analysis of the United States Food and Drug Administration Adverse Event Reporting System Database Based on the MY FAERS Platform. (PubMed, Nucleic Acid Ther) - "This study aimed to identify and quantify CAE-siRNA associated with U.S. Food and Drug Administration (FDA)-approved siRNA drugs (patisiran, givosiran, vutrisiran, inclisiran, and lumasiran) using real-world pharmacovigilance data, focusing on potential class-wide effects. This study identified clinically relevant CAE-siRNA, particularly hepatic toxicity for inclisiran, supporting enhanced monitoring. While disproportionality analyses are hypothesis generating, these findings underscore the need for targeted pharmacovigilance to optimize the safety of this promising drug class."

Adverse events • Journal • Back Pain • Fatigue • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Pain • Pain

Final Results of the ILLUMINATE-A Phase 3 Clinical Trial of Lumasiran for Primary Hyperoxaluria 1. (PubMed, Clin J Am Soc Nephrol) - P3 | "Lumasiran treatment for up to 60 months in ILLUMINATE-A was associated with sustained reductions in UOx excretion and plasma oxalate concentration, and encouraging clinical outcomes including stable eGFR in a population that would be expected to show eGFR decline, reduced kidney stone event rates, improved medullary nephrocalcinosis, and indications of improved quality of life."

Journal • P3 data • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

Primary Hyperoxaluria: Developing a Clinic Protocol (KIDNEY WEEK 2025) - "Is there a role for more genetic testing and stone risk assessment for transplant donors and recipients? Is there an application for lumasiran in patients outside of AGTX mutation PH1?"

Clinical • Chronic Kidney Disease • Genetic Disorders • Nephrology • Renal Disease • CST3

Comparison of Patients with Primary Hyperoxaluria 1 and Late-Stage CKD from the BONAPH1DE Registry and ILLUMINATE-C Lumasiran Trial (KIDNEY WEEK 2025) - P, P3 | "In ILLUM-C, POx was already reduced from BL at the time of iKT (19.2-64.5) and declined further post-iKT. Conclusion BPH1 and ILLUM-C data showed comparable POx reduction, eGFR improvement, and iKT outcomes with lumasiran treatment in both real-world and clinical trial studies."

Clinical • Late-breaking abstract • Chronic Kidney Disease • Nephrology

Final 60-Month Efficacy, Safety, and Kidney Stone Outcomes of a Phase 3 Trial of Lumasiran for Primary Hyperoxaluria Type 1 in Infants and Young Children (KIDNEY WEEK 2025) - P3 | "NC grade improved in most pts, and most did not have KSEs. The 4 pts with KSEs had UOx reductions and changes in NC grade consistent with those of other trial pts."

Clinical • P3 data • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Urolithiasis

Effect of Lumasiran on Long-Term Clinical Outcomes in Primary Hyperoxaluria Type 1: A Cohort Simulation Model (KIDNEY WEEK 2025) - P3 | "Lumasiran may also reduce the need for liver and kidney transplants, particularly in patients with preserved renal function. The results suggest that early lumasiran initiation may offer long-term clinical benefits, potentially altering the disease course in PH1 and improving lifetime patient outcomes."

Clinical • Clinical data • Chronic Kidney Disease • Genetic Disorders • Hepatology • Nephrology • Pediatrics • Renal Disease

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

Long-Term Lumasiran Treatment, Kidney Function, and Isolated Kidney Transplant Outcomes in Primary Hyperoxaluria Type 1 (KIDNEY WEEK 2025) - P2, P3 | "With 3 to 29 M of post-iKT follow-up as of M36, all 5 remained dialysis-free and continued lumasiran treatment. Conclusion Long-term lumasiran treatment resulted in minimal annual eGFR decline over 54 to 60 M in patients (baseline ages 3 M-60 Y) with PH1, in whom eGFR decline is expected, and effectively lowered POx to allow for iKT in some patients with end-stage kidney disease."

Nephrology • Transplantation

Kidney Survival in Patients with Primary Hyperoxaluria Type 1 Treated with Lumasiran Compared with Historical Controls (KIDNEY WEEK 2025) - "Lumasiran treatment was associated with reduced ESKD hazard compared with controls (HR [95% CI]: 0.049 [0.031-0.094], P <0.001). Conclusion These results suggest a clinically meaningful reduction in ESKD risk in PH1 pts with lumasiran treatment."

Clinical • Chronic Kidney Disease • Nephrology • Renal Calculi • Renal Disease

Late Diagnosis of Primary Hyperoxaluria Type 1 in a Geriatric Patient: Unique Clinical Course with Lumasiran (KIDNEY WEEK 2025) - "This outlook has improved with the advent of siRNA therapies targeting hepatic enzymes, thereby reducing UOx and POx levels. This case features the oldest known age for a PH1 diagnosis and demonstrates the effectiveness of lumasiran, including the unexpected clinical course of discontinuation of HD."

Clinical • Chronic Kidney Disease • Geriatric Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

Long-term efficacy, safety, and growth outcomes in the phase 3 ILLUMINATE-B trial of lumasiran for primary hyperoxaluria type 1 in infants and young children (ESPN 2025) - P3 | "Infants and young children in ILLUMINATE-B experienced a rapid and sustained reduction in urinary oxalate excretion, and with long-term lumasiran treatment achieved a normal expected linear growth per year and stable eGFR over 60 months. Lumasiran demonstrated consistent long-term safety in pediatric patients. Medullary nephrocalcinosis grade improved in most patients and kidney stone event rates were low."

Clinical • P3 data • Genetic Disorders • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Urolithiasis

GENETIC INSIGHTS AND THERAPEUTIC ADVANCES IN PRIMARY HYPEROXALURIA TYPE I: A THREE-PATIENT CASE SERIES (ESPN 2025) - "Because of its extremely low prevalence and nonspecific presentation, primary hyperoxaluria type I requires a high index of suspicion for timely recognition. Comprehensive genetic testing is essential to confirm the diagnosis, and the introduction of lumasiran therapy has significantly improved the prognosis for affected individuals."

Clinical • CNS Disorders • Epilepsy • Nephrology • Rare Diseases • Renal Calculi

PRIMARY HYPEROXALURIA TYPE 1 INHERITED AS A RESULT OF UNIPARENTAL DISOMY OF CHROMOSOME 2 (ESPN 2025) - "He was ineligible for the ILLUMINATE-B trial of the RNA interference drug Lumasiran (Oxlumo®)... This is the first reported case of PH1 due to paternal UPD of chromosome 2. It is important for clinicians to be aware of rarer patterns of inheritance that can give rise to autosomal recessive phenotypes and the importance of genetic testing of parents to confirm the inheritance pattern. The identification of an alternative inheritance pattern, such as UPD, has implications for genetic counselling and recurrence risk in future pregnancies."

Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

PRIMARY HYPEROXALURIA TYPE 1:EXPERIENCE OF A GENERAL PEDIATRICS DEPARTMENT (ESPN 2025) - "A request was submitted to the National Health Insurance Fund for the approval of Lumasiran for one patient, but no favorable response has been received yet... Primary hyperoxaluria type 1 remains a rare but serious genetic disorder with significant clinical variability. Early diagnosis is essential to initiate conservative management aimed at preserving renal function and slowing disease progression."

Clinical • Chronic Kidney Disease • Genetic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease

PRELIMINARY EXPERIENCE WITH LUMASIRAN IN RUSSIAN CHILDREN WITH PRIMARY HYPEROXALURIA 1 TYPE (ESPN 2025) - "Lumaziran therapy has shown promising results among Russian children with primary hyperoxaluria type 1."

Clinical • Chronic Kidney Disease • Gene Therapies • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

TARGETED GENE SILENCING WITH THE SIRNA DRUG LUMASIRAN: 3-YEAR FOLLOW-UP IN A 16-YEAR-OLD ADOLESCENT WITH PRIMARY HYPEROXALURIA TYPE 1 (ESPN 2025) - "PH1 is a heterogenous condition that does not always respond to conventional treatment, progressing to kidney failure and oxalosis. Lumasiran appears to be an effective new treatment that normalizes the oxalate urine excretion and could alters the unfavorable progression of the disease. Further research is required to determine possible side effects of long-term treatment with siRNA therapeutic agents."

Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

LUMASIRAN TREATMENT OUTCOMES IN INFANTS WITH PRIMARY HYPEROXALURIA TYPE 1 (ESPN 2025) - "Lumasiran treatment in infants with PH1 resulted in improvement in kidney function and urinary oxalate excretion but all patients had significant nephrocalcinosis and nephrolithiasis. The patients described escaped from their probable disease course of infantile oxalosis due to early treatment with lumasiran. Early diagnosis and treatment can change the disease course from severe infantile oxalosis to a milder form of kidney stone disease."

Clinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease

ISOLATED KIIDNEY TRANSPLANTATION UNDER LUMASIRAN THERAPY IN PRIMARY HYPEROXALURIA TYPE 1: A CASE REPORT (ESPN 2025) - "Our case suggests that iKT combined with Lumasiran therapy may be a viable option for pediatric patients with ESKD due to PH1. However, longer follow-up is necessary to assess the long-term effects of this therapy on the transplanted kidney. Further evidence in the pediatric population is needed to establish new therapeutic recommendations."

Case report • Clinical • Chronic Kidney Disease • Genetic Disorders • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi • Renal Disease • Transplantation

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