Viltepso (viltolarsen) / Nippon Shinyaku, National Center of Neurology and Psychiatry - LARVOL DELTA

Novel Therapeutic Frontiers in Duchenne Muscular Dystrophy: Gene Therapy, Exon Skipping, and Stem Cell Approaches. (PubMed, Curr Pharm Des) - "Recent treatment advancements provide renewed optimism via diverse innovative strategies, namely CRISPR-Cas9 gene editing, antisense oligonucleotide-mediated exon skipping (eteplirsen, golodirsen, viltolarsen, and casimersen), microdystrophin gene therapy using Adeno-Associated Viral (AAV) vectors, stop codon read-through therapy, and stem cell-based treatments. But difficulties with cost, immunogenicity, efficacy, and mutant specificity persist. Through multidisciplinary treatment and continuous scientific progress, individualized precision medicine that integrates therapies targeting secondary pathogenic pathways with dystrophin-restoration techniques can finally convert this devastating illness into a tolerable chronic ailment."

Journal • CNS Disorders • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy

Recalibrating Therapeutic Priorities for Duchenne Muscular Dystrophy: A Critical Synthesis of Approved and Emerging Strategies Through the Lens of an Underrepresented Population. (PubMed, Genes (Basel)) - "We argue that the conventional priority ordering (gene therapy first, exon-skipping second, standard care as background) does not hold up when weighed against patient-relevant outcomes and cost, and may reasonably be inverted for resource-limited systems. This is our interpretation of an indirect comparison, not an evidence-based clinical recommendation. On that reading, the highest-value investments for Central Asia are early molecular diagnosis, universal access to glucocorticoids and specialised physiotherapy, and individual-import pathways for ataluren, while AAV gene therapy is, in our view, a lower near-term priority until its durability and safety data improve."

Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

FDA-approved antisense oligonucleotide therapies for duchenne muscular dystrophy: current status and future outlook. (PubMed, RNA Biol) - "This review provides a comprehensive overview of the four FDA-approved ASO therapies - eteplirsen, golodirsen, viltolarsen, and casimersen - tracing their journey from pivotal clinical trials to post-marketing updates. Concurrently, intensive research is focused on developing next-generation ASOs to achieve enhanced therapeutic efficacy and definitive clinical outcomes. Elucidating the trajectory of research and development in this field offers profound insights for shaping future therapeutic strategies in rare diseases."

FDA event • Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Rare Diseases

Evaluation of the efficacy of Viltolarsen to DMD using muscular imaging (part 2) (JSNE 2026) - No abstract available

Clinical • Duchenne Muscular Dystrophy

EXPERT CONSENSUS ON TREATMENT GUIDANCE FOR FDA-APPROVED AND SECOND-GENERATION EXON-SKIPPING THERAPIES IN DUCHENE MUSCULAR DYSTROPHY (DMD): A RAND/UCLA MODIFIED DELPHI PANEL (ISPOR 2026) - "We aimed to characterize the current therapeutic landscape for DMD, including exon-skipping therapies, gene therapy, and givinostat, as well as emerging second-generation exon-skipping agents. Using the RAND/UCLA modified Delphi panel method, nine US experts (seven pediatric neurologists, two physical therapists) rated the likelihood of recommending FDA-approved therapies (eteplirsen, golodirsen, viltolarsen, casimersen, GT, givinostat) and the anticipated clinical value of investigational therapies with Phase 1/2 data (delpacibart zotadirsen, DYNE-251, WVE-N531, and NS-089/NCNP-02)... The panel reached consensus that approved exon-skipping therapies provide modest benefit, particularly in earlier stages, while early data suggest that second-generation exon-skippers may have the potential to offer greater functional improvement. However, trials remain in early stages, and the full risks and benefits of these therapies are not yet known. The findings highlight the rapidly..."

Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Safety and Efficacy of Viltolarsen in Duchenne Muscular Dystrophy: A Systematic Review and Meta-analysis (AAN 2026) - "However, its impact on dystrophin restoration remains inconclusive, with no clear dose-dependent advantage. Larger studies with extended follow-up are essential to determine its long-term efficacy and optimal dosing strategy."

Retrospective data • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Infectious Disease • Muscular Dystrophy

Treatment advances for Duchenne muscular dystrophy. (PubMed, Curr Opin Pediatr) - "This review summarizes the mechanism of action, key safety considerations and available evidence on motor function impact that these novel medications have demonstrated in DMD."

Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

A simple and highly sensitive LC-MS/MS bioanalytical method for phosphorodiamidate morpholino oligonucleotides in plasma. (PubMed, Bioanalysis) - "This method was also shown to be applicable to another phosphorodiamidate morpholino oligomer, ψM23D (+07-18). A simple and highly sensitive bioanalytical method for the determination of viltolarsen was established by optimizing RPLC and PPT, and the method was successfully applied to a phosphorodiamidate morpholino oligomers with a different sequence."

Journal

Motor Function Changes in Duchenne Muscular Dystrophy: A Case Series Using Conventional and Spinal Muscular Atrophy-Based Assessments During Viltolarsen Treatment. (PubMed, Pediatr Neurol) - "These findings suggest that CHOP-INTEND may capture subtle but clinically meaningful improvements in advanced-stage DMD. In conclusion, selecting stage-appropriate MFTs based on disease severity is important when evaluating treatment-related changes in patients with DMD."

Journal • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

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

Anti-PF4 antibodies are a potential mediator of antisense oligonucleotide (ASO)-induced thrombocytopenia. (ASH 2025) - "Twelve ASOs, Inotersen, Eplontersen,Olezarsen, Fomivirsen, Mipomersen, Tofersen, Nusinersen, Eteplirsen, Golodirsen, Viltolarsen,Casimersen (all FDA approved) and Volanesorsen (EMA approved) were evaluated in this study. With two ASOs, Fomivirsen and Eteplirsen, direct activation of platelets was noted. Studieswith additional ASOs revealed a novel immune mechanism involving ASO-PF4 complex formation andanti-PF4 antibody recognition that can plausibly mediate ASO-induced thrombocytopenia. These findingshighlight the key role PS linkages may play in ASO immunogenicity and provide a mechanistic frameworkfor risk mitigation in ASO drug design, supporting the safer development and broader application of ASOtherapeutics."

Hematological Disorders • Thrombocytopenia

Nephrotoxicity of Antisense Oligonucleotide Therapies in Duchenne Muscular Dystrophy: A Warning or a Challenge? (ISPOR-EU 2025) - "In the US Golodirsen, Viltolarsen, Eteplirsen and Casimersen are approved (conditionally) to treat DMD...Specific cases include: i) Drisapersen, terminated due to a poor benefit-risk profile, with notable renal toxicity, ii) Vesleteplirsen, associated with severe hypomagnesemia and hypokalemia... Patients with DMD treated with ONA require vigilant renal monitoring. Recommendations include regular assessment of renal biomarkers (e.g., proteinuria, creatinine), adjustment of corticosteroids, and preference for inactivated or conjugated vaccines."

Duchenne Muscular Dystrophy • Genetic Disorders • Inflammation • Muscular Dystrophy • Nephrology • Rare Diseases • Renal Disease

The Utilization, Reimbursement, and Cost of Targeted Therapies for Duchenne Muscular Dystrophy (DMD) in US Medicaid Programs: A Descriptive Trend Analysis from 2017 to 2022. (PubMed, Pharmaceut Med) - "The considerable rise in the utilization and spending of novel DMD drugs has imposed a significant burden on the Medicaid budget, underlining the need for policy measures to manage rising costs and maintain equal access to treatment."

Journal • Reimbursement • US reimbursement • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases. (PubMed, Methods Mol Biol) - "The US Food and Drug Administration (FDA) has granted accelerated approval for four AONs to skip a single DMD exon for treating patients with DMD: eteplirsen for exon 51 skipping, golodirsen and viltolarsen for exon 53 skipping, and casimersen for exon 45 skipping. Splice-modulating AONs have also been extensively tested in other inherited diseases, such as Usher syndrome, dystrophic epidermolysis bullosa (DEB), fibrodysplasia ossificans progressiva (FOP), and allergic diseases. This chapter will introduce the developmental status of exon skipping and splice-modulating therapies for genetic diseases."

Journal • Allergy • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Inherited Retinal Dystrophy • Muscular Dystrophy • Myositis • Myotonic Dystrophy • Ophthalmology

Tips to Design Effective Splice-Switching Antisense Oligonucleotides for Exon Skipping and Exon Inclusion. (PubMed, Methods Mol Biol) - "The approval of Exondys 51 (eteplirsen) and Spinraza (nusinersen) for the treatment of patients with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) was the most noteworthy accomplishment in 2016...The mechanism of mRNA splicing is highly complex, and the efficacy of AONs are often unpredictable. We will discuss the design of effective AONs for exon skipping and exon inclusion in this chapter."

Journal • Becker Muscular Dystrophy • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Myositis • Rare Diseases

Direct Reprogramming of Human DMD Fibroblasts into Myotubes for In Vitro Evaluation of Antisense-Mediated Exon Skipping and Exons 45-55 Skipping Accompanied by Rescue of Dystrophin Expression. (PubMed, Methods Mol Biol) - "To overcome these challenges, researchers can generate myofibers from patient fibroblast cells by transducing the cells with a viral vector containing MyoD, a myogenic regulatory factor. Here, we describe a methodology for assessing dystrophin exons 45-55 multiple skipping efficiency using antisense oligonucleotides in human muscle cells derived from DMD patient fibroblast cells."

Journal • Preclinical • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Creation of DMD Muscle Cell Model Using CRISPR-Cas9 Genome Editing to Test the Efficacy of Antisense-Mediated Exon Skipping. (PubMed, Methods Mol Biol) - "The approval of Exondys 51 (eteplirsen) targeting exon 51 was the most noteworthy accomplishment in 2016...Furthermore, many DMD mutations are very rare and it is hard to find a patient with a specific mutation for muscle biopsy in many cases. Here, we describe a novel approach to create an immortalized muscle cell line with a DMD deletion mutation using the human rhabdomyosarcoma (RD) cell line and the CRISPR/Cas9 system that can be used to test the efficacy of exon skipping."

Journal • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor

In Vivo Evaluation of Multiple Exon Skipping with Peptide-PMOs in Cardiac and Skeletal Muscles in Dystrophic Dogs. (PubMed, Methods Mol Biol) - "The FDA conditionally approved the first exon skipping AON, called eteplirsen (brand name ExonDys51), targeting exon 51 of the DMD gene, in late 2016...Although the success of multiple exon skipping in a DMD dog model has made a significant impact on the development of therapeutics for DMD, unmodified AONs such as phosphorodiamidate morpholino oligomers (PMOs) have little efficacy in cardiac muscles. Here, we describe the systemic delivery of a cocktail of peptide-conjugated PMOs (PPMOs) to skip multiple exons in both skeletal and cardiac muscles in dystrophic dogs and the evaluation of the efficacies and toxicity in vivo."

Journal • Preclinical • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Patient With Duchenne Muscular Dystrophy Who Tolerated Viltolarsen After Prior Anaphylaxis to Golodirsen. (PubMed, Muscle Nerve) - No abstract available

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Systemic Injection of Peptide-PMOs into Humanized DMD Mice and Detection by RT-PCR and ELISA. (PubMed, Methods Mol Biol) - "Researchers have previously relied on high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC/MS) methods for detecting PPMO uptake, but an enzyme-linked immunosorbent assay (ELISA) has been shown to have greater sensitivity. Here, we present methodologies to determine the uptake efficiency of a PPMO into the heart and efficacy of exon 51 skipping by a PPMO injected retro-orbitally into a humanized DMD mouse model via ELISA and RT-PCR, respectively."

Journal • Preclinical • Becker Muscular Dystrophy • Cardiovascular • Congestive Heart Failure • Duchenne Muscular Dystrophy • Genetic Disorders • Heart Failure • Muscular Dystrophy • Respiratory Diseases

Quantitative Evaluation of Exon Skipping in Immortalized Muscle Cells in Vitro. (PubMed, Methods Mol Biol) - "This is the case with eteplirsen, an exon 51-skipping AO that is the first and only FDA-approved drug for DMD to date...Aside from allowing for the quantitative evaluation of candidate AOs based on their exon skipping efficiency and dystrophin protein rescue levels, these immortalized cells are stable, pure, easy to grow, and not subject to confounding by senescence-related issues. This procedure enables a more reliable screening of AOs prior to their entry in clinical trials and greatly facilitates the search for more efficacious candidate exon skipping AOs for DMD treatment."

Journal • Preclinical • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Evolution and Breakthroughs in Exon Skipping and Splice Modulation: From Inception to Clinical Success. (PubMed, Methods Mol Biol) - "The FDA has approved several AO therapies using exon skipping, including eteplirsen, viltolarsen, casimersen, and golodirsen for DMD and nusinersen for SMA. This chapter explores the early history, evolution, and clinical applications of AO-based splice modulation therapies, focusing on exon skipping, one of the most developed strategies."

Journal • Developmental Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Exon-Skipping Using Antisense Oligonucleotides for Laminin-Alpha2-Deficient Muscular Dystrophy. (PubMed, Methods Mol Biol) - "These findings support the theory that PMO entry into fibres is dependent on the developmental stage in myogenesis rather than on dystrophin-deficient muscle membranes, and recommend a platform for the future development of PMO-mediated therapies for a variety of muscular disorders, such as LAMA2-MD, that involve active muscle regeneration. Herein, we describe the methods for PMO transfection/injection and the evaluation of the efficacy of exon-skipping in the laminin-α2-deficient dy3K/dy3K mouse model both in vitro and in vivo."

Journal • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • LAMA2

Real-world phosphorodiamidate morpholino oligomer treatment patterns in Duchenne muscular dystrophy: a claims-based analysis. (PubMed, J Comp Eff Res) - "Male patients with ≥1 claim for a PMO approved for DMD in the US (eteplirsen, casimersen, golodirsen and viltolarsen) were included. In an analysis of administrative claims data, adherence to PMO treatment for DMD was high. For patients with a gap in PMO claims, most subsequently re-initiated treatment, indicating lower discontinuation rates than previously reported."

Journal • Real-world evidence • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Assessment of the efficacy of viltolarsen using muscle mass index (JSNE 2025) - No abstract available

Clinical