Vyondys 53 (golodirsen) / 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

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

Efficacy and Safety of Golodirsen and Casimersen Compared With Placebo in Duchenne Muscular Dystrophy (ESSENCE) (ICNMD 2026) - P3 | "ESSENCE confirms the established safety profile of golodirsen and casimersen. The primary endpoint was not met in ESSENCE. A post hoc analysis and the totality of PMO evidence suggest the clinical benefits of golodirsen and casimersen."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Infectious Disease • Muscular Dystrophy • Novel Coronavirus Disease

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

Sarepta Announces FDA Acceptance of sNDAs for AMONDYS 45 and VYONDYS 53 (Investor Newswire) - "Sarepta Therapeutics...today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the supplemental New Drug Applications (sNDAs) for AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) for the treatment of Duchenne muscular dystrophy (DMD). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action data of February 28, 2027."

FDA filing • PDUFA • Duchenne 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

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

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

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=99 | Not yet recruiting | Sponsor: Sarepta Therapeutics | Initiation date: Feb 2016 ➔ Jun 2016

Trial initiation date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=99 | Not yet recruiting | Sponsor: Sarepta Therapeutics | Trial primary completion date: Apr 2018 ➔ Sep 2019

Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=99 | Not yet recruiting | Sponsor: Sarepta Therapeutics

New P3 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=222 | Active, not recruiting | Sponsor: Sarepta Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=222 | Recruiting | Sponsor: Sarepta Therapeutics | N=126 ➔ 222 | Trial completion date: Jun 2021 ➔ Jun 2023 | Trial primary completion date: Sep 2019 ➔ Jun 2022

Enrollment change • Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=222 | Recruiting | Sponsor: Sarepta Therapeutics | Active, not recruiting ➔ Recruiting

Enrollment open • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=126 | Recruiting | Sponsor: Sarepta Therapeutics | N=99 ➔ 126

Enrollment change • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=99 | Recruiting | Sponsor: Sarepta Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=228 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Trial primary completion date: Oct 2025 ➔ Nov 2024

Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=229 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Apr 2024 ➔ Oct 2025 | Trial primary completion date: Apr 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=229 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=222 | Recruiting | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: May 2023 ➔ Apr 2024 | Trial primary completion date: May 2022 ➔ Apr 2024

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • 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