Translarna (ataluren) / PTC Therapeutics - LARVOL DELTA

Cost-Utility Analysis of the Treatment With Ataluren Plus Standard of Care Compared With Standard of Care Alone in Patients With Duchenne Muscular Dystrophy in Brazil. (PubMed, Value Health Reg Issues) - "Ataluren plus SoC for treating nonsense mutation Duchenne muscular dystrophy patients was not a cost-effective intervention compared with SoC alone from the perspective of the Brazilian public health system."

HEOR • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Rare Diseases

Ataluren for the treatment of people living with nonsense mutation Duchenne muscular dystrophy: a plain language summary of Study 041. (PubMed, J Comp Eff Res) - P3 | "This study is the largest phase 3 clinical study of people living with nmDMD that has been done so far. ClinicalTrials.gov, NCT number: NCT03179631."

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

Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD) (clinicaltrials.gov) - P3 | N=270 | Completed | Sponsor: PTC Therapeutics | Enrolling by invitation ➔ Completed | Trial completion date: Apr 2025 ➔ Feb 2026 | Trial primary completion date: Apr 2025 ➔ Feb 2026

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

Efficacy and Safety of Ataluren in Duchenne Muscular Dystrophy due to Nonsense Mutation: A Systematic Review and Meta-analysis of Randomized Controlled Trials (AAN 2026) - "Ataluren demonstrates a favorable safety profile and a nonsignificant trend toward preserved ambulation in nmDMD. Although findings suggest potential clinical benefit, the limited number of RCTs and short follow-up durations warrant cautious interpretation. Larger, long-term, multicenter trials are required to better define ataluren's therapeutic role in nmDMD."

Retrospective data • Review • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases

Mutation type-specific transcriptomic signatures and readthrough therapy rescue in SMC1A-related developmental and epileptic encephalopathy. (PubMed, Epilepsia) - "These findings demonstrate that SMC1A-related epileptic encephalopathies are driven by variant-specific molecular mechanisms and highlight the therapeutic promise of ataluren for DEE85. The study supports further development of precision medicine strategies targeting nonsense variants in SMC1A, with potential implications for improving diagnosis, treatment, and quality of life in affected individuals."

Journal • CNS Disorders • Epilepsy • SMC1A

Beyond readthrough: ataluren restores mitochondrial function and reduces oxidative stress in FANCA-mutated cells via mTOR-DRP1 modulation. (PubMed, Cell Death Discov) - "Notably, these beneficial effects persisted under immune stimulation, where ataluren mitigated the metabolic and oxidative burden imposed by lymphocyte activation. Our findings unveil a pleiotropic role for ataluren that extends beyond its canonical readthrough activity, highlighting its potential as a metabolic modulator for FA and possibly other DNA repair-deficient disorders."

Journal • Aplastic Anemia • Hematological Disorders • Metabolic Disorders • FANCA • mTOR

Registry of Translarna (Ataluren) in Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) (clinicaltrials.gov) - P=N/A | N=316 | Completed | Sponsor: PTC Therapeutics | Active, not recruiting ➔ Completed

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

PTC Therapeutics Provides Regulatory Update on Translarna (PRNewswire) - "PTC Therapeutics, Inc...announced..that it has withdrawn the New Drug Application (NDA) resubmission for Translarna (ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy (DMD) following U.S. Food and Drug Administration (FDA) feedback on the application review...'FDA shared that based on its review to date, the data in the NDA submission are unlikely to meet the Agency's threshold of substantial evidence of effectiveness to support approval of Translarna.'"

FDA event • Duchenne Muscular Dystrophy

Patient reported outcome measures in spinal muscular atrophy and duchenne muscular dystrophy: review of instruments and their inclusion in clinical and regulatory processes. (PubMed, Neurol Sci) - "Despite the availability of PROMs, ObsROMs, and CROMs for SMA and DMD, their use in clinical trials and regulatory documents is limited and inconsistent. Greater standardization and systematic inclusion of these measures are needed to support patient-centered drug development and evaluation."

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

Beyond the stop: Oxadiazole TRIDs restore LRBA protein expression in nonsense-driven primary immunodeficiency. (PubMed, Mol Ther Nucleic Acids) - "Following the recent market withdrawal of ataluren, the only approved translational readthrough-inducing drug (TRID), there is an urgent need for alternative therapeutic options...However, network analysis revealed poor connectivity among differentially expressed proteins, with LRBA unrelated to any regulated cluster. These findings highlight the reported molecules as promising candidates for precision therapy in LRBA deficiency and shed light on the broader cellular impact of TRIDs."

Journal • Immunology • Primary Immunodeficiency

PTC…reported progress with its drug development pipeline. (Investing.com) - "The company reached alignment with the FDA on the design of a global Phase 3 trial for votoplam in Huntington’s disease, planned to initiate in the first half of 2026. The FDA confirmed openness to a potential Accelerated Approval pathway...The company’s New Drug Application for Translarna remains under FDA review."

FDA event • New P3 trial • Duchenne Muscular Dystrophy • Huntington's Disease

CFTR rescue in W1282X cystic fibrosis patient-derived intestinal organoids (PDIOs) mediated by translational readthrough-inducing drugs (TRIDs). (PubMed, Genet Med Open) - "Our studies highlighted the positive effect of NV848 on patient organoid swelling, improving CFTR channel function, whereas NV914 and NV930 did not induce organoid swelling, similar to PTC124 treatment. By leveraging patient-derived intestinal organoids, our findings showed that NV848, in combination with Elexacaftor-Tezacaftor-Ivacaftor and the nonsense-mediated mRNA decay inhibitor NMDI14, enhances CFTR activity. This contributes to the development of personalized therapies for individuals with rare CFTR variants, addressing a critical unmet need in cystic fibrosis treatment."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Duchenne Muscular Dystrophy in the Republic of North Ossetia-Alania: Epidemiological Study, Diagnostic Issues, and Treatment Prospects. (PubMed, Genes (Basel)) - "The heterogeneity of mutation spectrum across different populations underscores the influence of ethnic background. Consequently, this study highlights the importance of population-specific studies for improving DMD care."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Ataluren for Duchenne: how politics and social pressure undermined evidence-based decisions. (PubMed, BMJ Evid Based Med) - No abstract available

Journal

Evaluating ribosomal readthrough as a precision medicine strategy for restoring factor VIII expression in hemophilia a (ASH 2025) - "We testedaminoglycoside antibiotics (gentamicin, G418, ELX02) and non-aminoglycoside agents (ataluren and 2,6-diaminopurine [DAP]), each employing distinct mechanisms to induce ribosomal readthrough. Both aminoglycoside andnon-aminoglycoside compounds can restore partial FVIII expression in a mutation-specific manner. Theseresults support the further development of readthrough-based therapies as a cost-effective andaccessible treatment option for a subset of severe HA patients, potentially reducing their dependence onconventional replacement therapies."

Cystic Fibrosis • Duchenne Muscular Dystrophy • Genetic Disorders • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Muscular Dystrophy • Rare Diseases • Respiratory Diseases

Unraveling the interaction mechanism between the genetic disease drug Ataluren and eukaryotic codon recognition factor 1/ human serum albumin through spectroscopic and nuclear magnetic resonance approaches. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "In addition, a binding model of the interaction between PTC124 and eRF1/HSA was established by molecular simulation and STD-NMR. The binding model described in this paper explains the interaction mechanism between PTC124 and its utility and transport targets at the molecular level, which is helpful for the design and synthesis of new molecules related to PTC124 structure and based on its mechanism of action."

Journal • Genetic Disorders

Ataluren-Induced Functional Restoration of Neurofibromin in Fibroblasts From Neurofibromatosis Type 1 Patients With Nonsense Mutations. (PubMed, MedComm (2020)) - "Interestingly, AMPD3 can be an effective therapeutic target for NF1-associated diseases. Together, our study suggests that ataluren can be considered a therapeutic agent for some NF1NS/+ patients and contributes to expanding insights into NF1 therapy."

Journal • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

NHC-Catalyzed Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles from Amidoximes and Aldehydes. (PubMed, Org Lett) - "This study reports an efficient NHC-catalyzed [4 + 1] cyclization from accessible aldehydes and amidoximes to build it, concisely synthesizing tioxazafen, ataluren, and an mGluR5 antagonist. Broad substrate scope and gram-scale transformations confirm efficiency and practicality."

Journal

Natural history of patients with nonsense mutation Duchenne muscular dystrophy treated with ataluren in Spain. (PubMed, Acta Myol) - "Patients with DMD caused by nonsense mutations present a similar phenotype to those with DMD with other types of mutations. Patients treated with ataluren delayed the loss of ambulation and appeared to maintain upper limb and respiratory function better than those not treated with ataluren."

Journal • Retrospective data • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Key Clinical and Regulatory Updates (PTC Therapeutics Press Release) - "Additional Sephience marketing authorization reviews ongoing including in Japan where decision is expected in Q4 2025; FDA meeting for votoplam Huntington's disease program planned for Q4; FDA meeting planned for vatiquinone Friedreich's ataxia program in Q4; Translarna NDA remains under FDA review."

FDA event • Japan filing • Duchenne Muscular Dystrophy • Friedreich ataxia • Huntington's Disease • Phenylketonuria

TREM2-Mediated Cholesterol Efflux in Macrophages Inhibits Anti-Tumor Immunity via Limitation of CD4+ T and NK Cells. (PubMed, Adv Sci (Weinh)) - "After screening food and drug administration (FDA)-approved drugs, bortezomib and ataluren are found to effectively inhibit TREM2 expression in TAMs, indicating a potential therapeutic strategy against TREM2. This study elucidates the mechanism by which TREM2 shapes the immunosuppressive microenvironment and promotes tumorigenesis, highlighting TREM2 as a target for cancer immunotherapy."

IO biomarker • Journal • Lung Cancer • Oncology • Solid Tumor • ABCA1 • CD4 • CX3CL1 • TREM2

Duchenne and Becker Muscular Dystrophies in Romania: a 10-year Retrospective Study. (PubMed, Eur J Paediatr Neurol) - "For exceptions from the rule, the involvement of different isoforms, binding domains, structural domains, and the disturbance of the three-dimensional structure of the rod domain were not reliable indicators of the phenotype. 12.9 % of all patients had nonsense mutations with a DMD phenotype that could benefit from Ataluren treatment within the National Treatment Program, and 15 % were eligible for exon-skipping therapies, with exon 51 having the broadest applicability (7.1 %)."

Journal • Retrospective data • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Pediatrics • Psychiatry • Rare Diseases

CC-90009, a modulator of Cereblon E3 ligase, restores W1282X and G542X CFTR nonsense variants in rectal organoids (NACFC 2025) - "Furthermore, the combination with the aminoglycosides G418 or ELX-02 but not with PTC124 further enhances their mutual effects, remarkably increasing the PTC readthrough response. In conclusion, the eRF3a degrader CC-90009, alone or combined with other compounds, could represent a promising therapeutic approach to rescue CFTR nonsense variants. Additional candidate read-through molecules are currently under study using our intestinal organoid-based screening and validation platform."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • Targeted Protein Degradation • CFTR • CRBN • GSPT1

Investigating the combinatorial effects of ACE-tRNAs and small molecules to suppress CF-causing nonsense mutations (NACFC 2025) - "Figure 1 (abstract 279): Simultaneous AZD-7648 and UbVa treatment enhances gene insertion in primary ABCs using the dual-vector strategy...Additionally, several small molecules with differing mechanisms of actions have been shown to readthrough PTCs, such as G418, PTC124, SRI-41315 and CC-90009... Currently, experiments to determine the optimal ACE-tRNA + small molecule combinations are being performed."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR

High-throughput screening methods to discover new ribosomal inhibitors that rescue multiple classes of CFTR variants (NACFC 2025) - "Studies included treatment comparisons to established inhibitors of translation (G418, PTC-124, ELX-02, Escin) and CFTR modulators (elexacaftor-tezacaftor-ivacaftor, vanzacaftor-tezacaftor-deutivacaftor). Partial depletion of RPL12 levels represents a feasible strategy for CFTR modulation, which may be applicable to CFTR genotypes refractory to available clinical interventions. Our work serves as a foundation from which future investigations may be pursued to examine efficacy and tolerability of anti-RPL12 compounds or ASOs delivered to CF animal models."

CFTR