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

Histopathologic Characterization of Cutaneous Oxalosis Mimicking Calciphylaxis: Diagnostic Pitfalls and Polarized Light Evaluation. (PubMed, J Cutan Pathol) - "Repeated skin biopsies, however, confirmed cutaneous oxalosis despite perceived stable metabolic control with lumasiran. This case highlights the complexities and challenges in the diagnosis of cutaneous manifestations of chronic kidney disease and emphasizes the importance of histopathologic evaluation, even if the patient's primary hyperoxaluria is believed to be well-controlled."

Journal • Calciphylaxis • Chronic Kidney Disease • Nephrology • Rare Diseases • Renal Disease

Primary hyperoxaluria type 1-current practice in the siRNA era: an ERA Genes & Kidney Working Group survey. (PubMed, Clin Kidney J) - "The advent of targeted treatment opportunities for PH1 comes with an increased need to provide guidance to the field. Filling the existing gaps will ensure that a growing number of patients get access to optimal care and novel life-changing therapies."

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

Lumasiran Treatment and Isolated Kidney Transplantation in Primary Hyperoxaluria 1 and Late-Stage Chronic Kidney Disease (ATC 2026) - P, P3 | "In this group of pts with PH1 and late-stage CKD, lumasiran was associated with reduced POx pre- and post-iKT, with concordant findings across real-world and clinical trial settings. These results suggest that lumasiran can facilitate iKT in PH1 pts by reducing oxalate burden."

Late-breaking abstract • Chronic Kidney Disease • Nephrology • Renal Disease • Transplantation

How OXLUMO Makes a Difference: Clinical Data and Real Patient Cases (ATC 2026) - "Examine OXLUMO's efficacy and safety data and explore how these findings may inform clinical decision-making. This session features practical insights from 2 real patient case reports, highlighting how OXLUMO may be used across different patient presentations and care settings TypesProduct Theater"

Clinical data

Impact of Baseline Urinary Oxalate on Response to Lumasiran Treatment in the ILLUMINATE-A Study of Primary Hyperoxaluria Type 1 (ERA 2026) - No abstract available

Nephrology

Successful Recovery of Graft Function and Normalization of Post‑Transplant Oxalate Levels With Lumasiran in a Patient With Primary Hyperoxaluria Type1 (ERA 2026) - "Our center's experience suggests that integrating these therapies with metabolic monitoring may reduce post‑transplant oxalate burden and improve both graft and patient survival, even in patients who have just become dialysis-dependent because of oxalate nephropathy recurrence in the graft and that were deemed non-responsive before transplantation. Why this case is exeptional Our case shows that lumasiran may still be effective even after a kidney transplant recipient appears to lose graft function and returns to dialysis due to post‑transplant recurrence of oxalate nephropathy, including in situations where lumasiran had been considered ineffective during the pre‑transplant course"

Clinical • Post-transplantation • Cardiovascular • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Thrombosis • Transplantation

Final, 60-Month Results of ILLUMINATE-C, Evaluating Lumasiran Treatment of Primary Hyperoxaluria Type 1 in Patients With Advanced Kidney Disease (ERA 2026) - No abstract available

Clinical • Metastases • Nephrology • Renal Disease

Prymary hyperoxaluria type 1: Mid term treatment with Lumasiran (ERA 2026) - "There was a marked reduction in 24-hour UOx in the older child (Month 6: -80% Month 12: -74%) and a reduction in the urinary oxalate/creatine ratio in the second child (Month 6: -77% Month 12: -81%). eGFR increased from 68 ml/min/1.73 at baseline to 112 al 12 months. No change in the renal ultrasound at 12 months."

Genetic Disorders • Infectious Disease • Metabolic Disorders • Nephrology

Long-Term Lumasiran Treatment and Nephrocalcinosis Outcomes in Primary Hyperoxaluria Type 1: A Post Hoc Analysis of ILLUMINATE-A (ERA 2026) - P2, P3 | "These findings support sustained long-term reductions in oxalate levels in patients with PH1 treated with lumasiran and underscore the possibility of associated long-term improvement in NC. Image"

Retrospective data • Metabolic Disorders • Nephrology • Renal Calculi

Diastereomer separation of phosphorothioate oligonucleotides via conformationally stabilizing ion pairs in reversed-phase liquid chromatography. (PubMed, J Chromatogr A) - "In this study, we showcase the power of alkyldiamines (ADs) as a new class of ion pairing reagents for oligonucleotide diastereomer separation using two FDA-approved small interfering RNA (siRNA) compounds, Lumasiran and Vutrisiran, and single-stranded sequences derived from the antisense strand of Lumasiran, as model compounds. To best of our knowledge, this is the first time that ion pairing reagents with conformation-stabilizing effect are used for both single- and double-stranded oligonucleotide analysis. This work enriches the analytical toolkit for oligonucleotide characterization and may enable batch-to-batch diastereomer distribution monitoring in synthetic phosphorothioate oligonucleotides."

Journal

A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics. (PubMed, Mol Ther Nucleic Acids) - "This platform integrates preclinical and clinical data from all seven FDA-approved GalNAc-siRNA drugs-fitusiran, givosiran, inclisiran, lumasiran, vutrisiran, nedosiran, and plozasiran-spanning multiple species (mouse, rat, monkey, and human). The platform successfully predicted the PK and simulated the PD profiles of SAL0132 in humans, which demonstrated model-informed strategies to support efficient drug development of this modality. In conclusion, this platform enables users to predict GalNAc-siRNA PK/PD profiles across species by inputting specific model parameters, providing a powerful resource to guide the development of next-generation GalNAc-siRNA therapeutics."

Journal

Isolated Kidney Transplant in Primary Hyperoxaluria-1 Enabled by Small Interfering RNA (siRNA) Therapy. Is It Time for Change? Case Report and Review of the Literature. (PubMed, Pediatr Transplant) - "This report enriches the limited experience of RNAi-enabled kidney-only transplantation in PH1. RNA interference therapy has the potential to challenge the current standard of dual liver and kidney transplantation in children and young adults with this devastating disease but requires uninterrupted access to the drug with individualized, eGFR and oxalate level adjusted dosing, continued vigilance, and reporting of long-term outcomes."

Journal • Review • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Calculi • Transplantation • LDHA

Bilateral staghorn calculi in primary hyperoxaluria type 1. (PubMed, Kidney Int) - No abstract available

Journal • Nephrology

Descriptive Analysis of Real-World Enrollment Data of Pediatric and Adult Patients From a Global Primary Hyperoxaluria Type 1 Registry (BONAPH1DE) (PAS 2026) - P | "From December 13, 2021 to November 18, 2024, 82 pediatric and 42 adult pts of 138 enrolled had lumasiran treatment history. Family history of PH1 was reported for 39 (48%) pediatric and 16 (38%) adult pts. Twenty-one (26%) pediatric and 22 (52%) adult pts had a pyridoxine-responsive–associated genotype (PR/PR or PR/-)."

Clinical • Real-world • Real-world evidence • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Pediatrics • Renal Calculi

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 (PAS 2026) - No abstract available

Clinical • P3 data • Nephrology

CLINICAL RESPONSE TO LUMASIRAN IN A PH1 PATIENT ON HEMODIALYSIS: CHALLENGES IN OXALATE CONTROL UNDER LIMITED DIALYSIS ACCESS (ISN-WCN 2026) - "These findings underscore the need for individualized dialysis strategies and support the role of RNAi therapies in mitigating disparities in care delivery. In resource-limited settings, optimizing treatment outcomes requires not only access to novel therapies but also systemic improvements in dialysis infrastructure."

Clinical • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

KIDNEY-ALONE TRANSPLANTATION WHILE ON SIRNA THERAPY FOR PRIMARY HYPEROXALURIA TYPE 1: A MULTINATIONAL RETROSPECTIVE CASE SERIES FROM THE PH1NITX WORKING GROUP (ISN-WCN 2026) - "Lumasiran and nedosiran, which inhibit glycolate oxidase and lactate dehydrogenase A, respectively, effectively reduce oxalate burden. Summary of general characteristics:Abbreviations: AGXT, alanine-glyoxylate aminotransferase gene; CLKTx, combined liver-kidney transplantation; GFR, glomerular filtration rate; IHD, intermittent hemodialysis; IQR, interquartile range; PD, peritoneal dialysis; siRNA, small interfering ribonucleic acid.Conclusion This large international case series suggests that KATx, when paired with siRNA therapy, is emerging as a compelling alternative to LKTx for PH1 patients with KF - even when the diagnosis is made post-transplant. Based on these favorable outcomes and our collective experiences, we offer a practical checklist to assist with pre- and post-transplant planning and recommend continued vigilance for both known and unexpected complications as the treatment paradigm evolves."

Retrospective data • Genetic Disorders • Infectious Disease • Nephrology • Transplantation • LDHA

Advances in siRNA-Loaded Nanocarriers: Harnessing Cutting-Edge Technologies for Precision Cancer Treatment. (PubMed, Curr Pharm Des) - "siRNA-based therapeutics represent a promising strategy for targeted cancer therapy due to their high specificity and ability to reduce off-target toxicity. Nanocarrier systems have greatly enhanced their clinical viability. However, continued efforts are required to overcome biological barriers and facilitate clinical translation. This review also summarizes FDA-approved siRNA-based drugs such as Onpattro®, Leqvio®, Givlaari®, Oxlumo®, Tavnelis®, and Amvuttra®, underscoring the clinical potential of RNAi-based therapies."

Journal • Oncology

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