Exondys 51 (eteplirsen) / Sarepta Therapeutics - 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

Exon-skipping therapies for DMD in Kazakhstan: Progress and challenges. (PubMed, J Neuromuscul Dis) - "Functional outcomes (Scott scale, Vignos scale, 6-minute walk test, and 4-stair climb) were extracted and analyzed.ResultsA total of 46 patients received eteplirsen (n = 24), golodirsen (n = 14), and casimersen (n = 8). Functional assessments showed that patients were generally stable or improved over time. Approximately one-third of patients experienced treatment interruptions or were anticipated to be unable to maintain their prescribed exon-skipping therapy due to inadequate funding.ConclusionsThese data reflect the challenges patients with DMD experience in Kazakhstan, and the need for improved funding to maximize the therapeutic potential of exon-skipping therapies."

Journal • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

An antisense method for efficient exon skipping and its application to Duchenne muscular dystrophy. (PubMed, Proc Natl Acad Sci U S A) - "Particularly, an 8-nt tail, when appended to sequences targeting DMD exon 51, elicited a pronounced increase in exon skipping in mouse models, restored dystrophin expression in muscle tissues and improved the phenotype, without obvious signs of toxicity. The lead ASO further demonstrated a marked exon-skipping effect and an overall safe profile in monkeys. Our data establish a valuable platform technology for RNA-targeted therapeutics."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • 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

Case Report: The effect of early initiation of eteplirsen treatment on the cardiac and motor disease course in an individual with Duchenne muscular dystrophy. (PubMed, Front Pediatr) - "At 24 months of age, weekly intravenous eteplirsen therapy was initiated, along with enalapril to manage cardiac symptoms. Despite persistent hyperlordosis and waddling gait, his 6-minute walk test remained stable. To our knowledge, this is the first documented case of DMD reporting cardiac outcomes after eteplirsen treatment in a patient as young as 24 months of age."

Journal • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Phase 2 Study of Vesleteplirsen in Patients With Duchenne Muscular Dystrophy: MOMENTUM Part B Results (ICNMD 2026) - P1/2, P2 | "Although vesleteplirsen treatment resulted in a statistically significant increase in dystrophin expression, meeting the primary biological endpoint, MOMENTUM was terminated early due to long-term safety concerns and the evolving therapeutic landscape in DMD. Funding: Sarepta Therapeutics, Inc."

Clinical • P2 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Orthogonal Methods Demonstrate Pharmacodynamic Responses in Duchenne Muscular Dystrophy Patients Treated with BMN 351 (ICNMD 2026) - P1/2 | "Background: BMN 351 is an antisense oligonucleotide therapeutic designed to exclude DMD exon 51 during mRNA splicing in muscle and induce synthesis of functional, near full-length dystrophin protein in amenable patients with Duchenne muscular dystrophy (DMD). Together, the data from these orthogonal methods provide a robust data set demonstrating early patient responses and support the potential for clinical benefit in patients treated with BMN 351."

Clinical • PK/PD data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Preclinical Efficacy of ENTR-601-51 for the Treatment of Exon 51 Skip-Amenable Duchenne Muscular Dystrophy (ICNMD 2026) - "Preclinical studies have established the therapeutic potential of ENTR-601-44, ENTR-601-45, and ENTR-601-50 for patients with exon 44, 45, and 50 skip-amenable DMD, respectively...mdx gastrocnemius muscle were also measured. In patient-derived skeletal muscle cell lines with DMD exon 51 skip-amenable mutations, treatment with ENTR-601-51 resulted in robust, dose-dependent exon 51 skipping and dystrophin protein expression... These results demonstrate that ENTR-601-51 is efficiently delivered to skeletal and cardiac muscle in vivo, thereby producing durable exon skipping and functional dystrophin protein that are able to rescue muscle contractile function in a relevant mouse model of human DMD . These findings support further evaluation of ENTR-601-51 in patients with DMD amenable to exon 51 skipping."

Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • HSP90AA1

Patient Experiences With DMD and Impacts of PMO Therapies - Interviews With Caregivers From REAL-DMD (ICNMD 2026) - "Caregivers from REAL-DMD whose patients are receiving casimersen, eteplirsen, or golodirsen participated in one-on-one semi structured interviews to describe experiences following PMO treatment initiation and to assess the meaningfulness of such experiences. This interview study highlighted the profound impact of DMD on children's lives, while also highlighting resilience families demonstrate in navigating its challenges. Caregivers' perspectives reveal that the PMO therapies are valued for their perceived ability to preserve physical function and maintain disease stability, while also providing a sense of hope in the face of a progressive disease. Such caregiver voices are important for identifying meaningful outcomes reflecting both physical functioning and the broader quality-of-life dimensions that matter to families."

Clinical • Interview • CNS Disorders • Duchenne Muscular Dystrophy • 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

A Real-World Target Trial Emulation of Eteplirsen, Casimersen, and Golodirsen to Evaluate Survival Among Patients with Duchenne Muscular Dystrophy. (PubMed, Adv Ther) - "The relative risk reduction in mortality suggests a promising treatment effect of PMO + GCs versus GCs-only, which should be confirmed in future studies with longer follow-up."

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

35-amino acids Truncation of Staphylococcus aureus Cas9 Protein by A Size-Minimization via Integral Library Evolution (S.M.I.L.E) Strategy (ASGCT 2026) - "Two weeks later, the corresponding muscle tissues were collected for skipping efficiency analysis of DMD exon 51...Conclusion We successfully developed a functional and truncated SaCas9 via SMILE technology, which may confer improved delivery by AAV. In addition, SMILE provides a feasible approach for the miniaturization of large proteins with complex structures through the deletion of several amino acids and minimal structural perturbation."

Gene Therapies

An all-in-one AAV cytosine base editor therapy in Duchenne Muscular Dystrophy (ASGCT 2026) - "All-in-one AID CBE has been developed for DMD exon 51, exon 53, and exon 50 skipping therapy...The animal data will be expected at the upcoming conference. Conclusion All-in-one AAV deliverable Base editor can greatly expand the application scope in genetic diseases by different tissue-specific AAVs."

Duchenne Muscular Dystrophy • Genetic Disorders • 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

IMPACT OF ETEPLIRSEN TREATMENT INITIATION DELAYS ON LOSS OF AMBULATION INCIDENCE AMONG AMBULATORY PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY (ISPOR 2026) - "Extrapolating evidence from real world studies, this model suggests eteplirsen reduces the cumulative LoA incidence versus SoC alone regardless of timing. However, even a 6-month delay in treatment initiation would increase the cumulative LoA incidence within 5 years versus immediate treatment, and this impact worsens with longer delays."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

MODELING THE LIFETIME BENEFITS OF ETEPLIRSEN IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY (ISPOR 2026) - "This model complements the totality of RWE for eteplirsen by estimating potential lifetime benefits in patients initiating treatment at an early age, increasing ambulatory time and extending survival."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Advancements from the EVOLVE study for assessing real-world experience with eteplirsen, golodirsen and casimersen for the treatment of DMD. (PubMed, J Comp Eff Res) - P | " Consistent with the safety findings from previous clinical trials, eteplirsen, golodirsen and casimersen showed favorable safety profiles in patients with DMD in routine clinical practice. EVOLVE will continue to describe long-term clinical outcomes Clinical Trial Registration Number: NCT06606340."

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

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

Superior editing efficiency and small size of CRISPR/hfCas12Max for gene and cell therapy applications (ESGCT 2024) - "After systemic delivery of a single all-in-one AAV vector that contained hfCas12Max along with a gRNA targeting the splice donor (SD) site of human DMD exon 51 to the Duchenne Muscular Dystrophy (DMD) mouse model, we observed efficient restoration of dystrophin expression...Our findings suggest that hfCas12Max, with its robust editing activity and high specificity, is a promising tool for safer and more effective gene and cell therapy treatments. Synthetic guide RNAs and purified nuclease for hfCas12Max are now readily available for CRISPR medicine developers through Synthego Corporation, USA, as part of a strategic partnership with HuidaGene to enhance the accessibility and efficiency of the CRISPR tools."

Amyotrophic Lateral Sclerosis • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Muscular Dystrophy

CRISPR/hfCas12Max-based single-cut gene-editing therapy restores dystrophin expression and muscle performance in mouse models of Duchenne muscular dystrophy to support the initiation of MUSCLE clinical trial (ESGCT 2024) - "The antisense oligonucleotide medicines, known as Eteplirsen or Casimersen, have been approved to treat DMD patients with exon 45–55 hotspot region mutations. Our novel discovery of hfCas12Max nuclease and rigorously designed and executed in vitro and in vivo tests support the clinical development of an ‘all-in-one’ AAV with the CRISPR/hfCas12Max gene-editing therapy for DMD patients. The U.S. FDA has granted orphan drug and rare pediatric disease designations to HG302 for treating DMD."

Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Pediatrics

Development and future prospects of exon-skipping therapy for Duchenne muscular dystrophy. (PubMed, Brain Dev) - "In 2016, eteplirsen, which induces exon 51 skipping, received accelerated approval in the United States...The establishment of an early diagnostic system may also need to be considered. The present review outlines the development and future challenges of exon-skipping therapy for DMD and the expansion of splice-switching therapy (a therapy that uses AS-oligo to control splicing), including exon-skipping therapy, to other diseases."

Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

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