Translarna (ataluren) / PTC Therap - LARVOL DELTA

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

Molecular treatment options for patients carrying KIAA0586/TALPID3 variants. (PubMed, Mol Ther Nucleic Acids) - "These cellular defects were responsive to treatments with RNA-based therapeutics and/or readthrough agents (RTAs). Our results highlight the potential of addressing mutations and molecular defects associated with KIAA0586/TALPID3 sequence alterations as future perspectives toward treatments of patients."

Journal • PCM1

Ataluren improves hematopoietic and pancreatic disorders in Shwachman-Diamond syndrome patients: a compassionate program case-series. (PubMed, Nat Commun) - "The exocrine pancreatic function also improved. Although the reduced sample size may represent a major limitation of this work, our findings strongly encourages the further clinical development of ataluren to treat SDS."

Journal • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Pancreatitis

Biocatalytic heterocycle synthesis enabled by n-halogenation by vanadium-dependent haloperoxidases (ACS-Fall 2025) - "This biocatalytic platform was subsequently applied to the conversion of N-acylamidines to 1,2,4-oxadiazoles in high yield and chemoselectivity. Finally, the synthetic potential of this biotechnology is demonstrated in its extension to N-N bond formation and its application in the chemoenzymatic synthesis of Ataluren, a treatment for Duchenne muscular dystrophy."

Developmental Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Confirmatory long-term efficacy and safety results of ataluren in patients with nmDMD from Study 041, an international, randomized, double-blind, placebo-controlled, Phase III trial. (PubMed, J Comp Eff Res) - "Ataluren was well tolerated (serious adverse events: ataluren, 7.1%; placebo, 6.8%); no deaths occurred. Long-term ataluren treatment has a favorable benefit-risk profile, slowing motor function decline in the largest phase III nmDMD study to date."

Clinical • Journal • P3 data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Discovery of novel triaryl derivatives as readthrough-inducing drugs (ACS-Fall 2025) - "Furthermore, KY-516, a representative compound in which the B and C rings of lead compound 1 were converted, showed 460-fold higher activity than ataluren in the luciferase assay and significantly increased enzyme activity in mutant IDUA transgenic cells at 0.1 μM. In conclusion, KY-516, a novel triaryl derivative, was shown to possess potent readthrough activity, indicating its potential as a treatment for Hurler syndrome."

Cystic Fibrosis • Genetic Disorders • Hurler Syndrome • Immunology • Muscular Dystrophy • Rare Diseases • Respiratory Diseases • IDUA

Development of novel readthrough-inducing agents for nonsense mutation-type mucopolysaccharidosis type I (Hurler syndrome) (ACS-Fall 2025) - "Readthrough-inducing agents, such as ataluren, have been developed to suppress premature translation termination and restore IDUA enzyme expression; however, their efficacy remains suboptimal...These results suggest that chromenopyridine derivatives with appropriate modifications at the N2 and 3 positions, along with A-ring modifications, serve as a promising scaffold for novel readthrough-inducing agents. KY-640 exhibited potent readthrough-inducing activity and, thus, has potential as a therapeutic candidate for Hurler syndrome."

Genetic Disorders • Hurler Syndrome • IDUA

Key Clinical and Regulatory Milestones (PRNewswire) - "NDA reviews for vatiquinone (Friedreich's ataxia) and Translarna (nonsense mutation DMD) are ongoing, with regulatory action date of August 19, 2025 for vatiquinone...In May 2025, reported positive Phase 2 PIVOT-HD study results for votoplam (PTC518) in Huntington's Disease patients. PTC continues to collaborate with Novartis on next steps and aims to meet with FDA in Q4 2025 to discuss Phase 3 clinical trial design and potential accelerated approval pathway."

Clinical protocol • New P3 trial • PDUFA • Duchenne Muscular Dystrophy • Friedreich ataxia • Huntington's Disease

Beyond the bench: Revitalizing ataluren development for rare genetic disorders. (PubMed, Mol Ther) - No abstract available

Journal • Genetic Disorders

Development of translational read-through-inducing drugs as novel therapeutic options for patients with Fanconi anemia. (PubMed, Cell Death Discov) - "Amlexanox, an anti-inflammatory drug, also promotes read-through of premature stop codons caused by nonsense mutations. This study represents a milestone of drug development for FA as it paves the way for clinical development of TRIDs, indicating ataluren as a promising approach to address the genetic instability and reduce the risk of malignant transformation in FA cells. Moreover, these results highlight the importance of a reliable experimental pipeline to assess whether minimal protein rescue via translational read-through can yield meaningful phenotypic rescue."

Journal • Anemia • Hematological Disorders • Pediatrics • FANCA • FANCC • FANCF • LMNB1 • STAT2

CFTR rescue in a G542X nonsense mouse model of cystic fibrosis: investigating the mechanism of action and activity of translational readthrough-inducing drugs (ECFS 2025) - "These findings highlight the therapeutic potential of NV914 and related compounds for treating CF caused by nonsense mutations, paving the way for further development of effective targeted therapies."

Preclinical • Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • CFTR • EEF1A1

Opinion of the Italian Association of Myology on Ataluren for the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy. (PubMed, Drugs R D) - "Furthermore, a long-term registry of "real-world" ataluren treatment data (Strategic Targeting of Registries and Database of Excellence, STRIDE), in addition to confirming a reassuring safety profile, suggested a prolonged maintenance of ambulatory, upper limb, and respiratory function. We deem that a withdrawal of ataluren from the European market would harm not only patients with nonsense mutation Duchenne muscular dystrophy, but the whole neuromuscular field, in which clinical trials are challenging because of the heterogenous complex slow-progressing nature of the disorders."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Engineering a Compact Gene Switch for Temporal Control of AAV-CRISPR Gene Editing (ASGCT 2025) - "TREAD consists of a nine-nucleotide DNA effector sequence containing the TGA stop codon, designed to be inserted into the gene of interest, and a chemical inducer (such as gentamicin or PTC124) that enhances TGA readthrough, effectively "switching on" gene expression. Our ongoing research is focused on creating an inducible AAV-CRISPR gene editing therapy for cardiomyopathy associated with Friedreich ataxia, leveraging TREAD in conjunction with our newly engineered cardiotropic vector AAV.CPP.16. Disease Focus of Abstract:None"

Ataxia • Cardiomyopathy • Cardiovascular • Friedreich ataxia • Gene Therapies • Genetic Disorders • Movement Disorders

Administrative healthcare data to identify and describe patients with rare diseases: the case of Duchenne muscular dystrophy. (PubMed, Recenti Prog Med) - "This study of administrative data has identified patients potentially affected by DMD, a rare disease, from a large sample of INHS beneficiaries, and assessed their healthcare pathway. This is useful for regulatory purposes and for improved access to emerging innovative therapies."

Journal • Observational data • Retrospective data • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Orthopedics • Rare Diseases • Respiratory Diseases

A Precision Medicine Approach to Primary Immunodeficiency Disease: Ataluren Strikes Nonsense Mutations Once Again. (PubMed, Mol Ther) - "Our results provide a proof-of-concept demonstrating that ataluren, can rescue LRBA expression in PID. This work highlights the potential for personalized precision medicine approaches to be exploited for different genetic diseases due to premature termination codons."

Journal • Genetic Disorders • Immunology • Primary Immunodeficiency