Trial reportJournal of neurology2022
Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update.
Trial report in Journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (NEURO-TTR Study)
An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (FAP)
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis.Journal of the peripheral nervous system : JPNS · 2026Article
- Development and Clinical Applications of Antisense Oligonucleotide Gapmers.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Unravelling the myriad physiologic roles of transthyretin: critical considerations for treating transthyretin amyloidosis.Annals of medicine · 2025Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Serum Biomarkers in Transthyretin Amyloidosis: An Overview of Neurofilaments, Cardiac, Renal, and Gastrointestinal Involvement.Neurology and therapy · 2025Review
- Transthyretin Cardiac Amyloidosis: Current and Emerging Therapies.Current cardiology reports · 2025Review
- Clinical utility of neurofilament light chain as a biomarker for disease onset and progression in hereditary transthyretin amyloidosis.Frontiers in neurology · 2025Article
- Hemodynamics in Left-Sided Cardiomyopathies.Reviews in cardiovascular medicine · 2024Review
- Transthyretin amyloidosis in spinal canal stenosis: A systematic review.Journal of orthopaedics · 2024Review
- Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease.Biomolecules · 2024Review
- Anti-MAG neuropathy: historical aspects, clinical-pathological correlations, and considerations for future therapeutical trials.Arquivos de neuro-psiquiatria · 2024Review
- Review
- Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro.Arquivos de neuro-psiquiatria · 2024Article
- Nerve pathology of microangiopathy and thromboinflammation in hereditary transthyretin amyloidosis.Annals of clinical and translational neurology · 2024Article
- Novel Therapeutic Approaches in Inherited Neuropathies: A Systematic Review.Pharmaceutics · 2023Review
- RNA Targeting and Gene Editing Strategies for Transthyretin Amyloidosis.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- What Can RNA-Based Therapy Do for Monogenic Diseases?Pharmaceutics · 2023Review
- World Heart Federation Consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM).Global heart · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 18 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years.
methodsPatients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004.
resultsIn the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen-inotersen) and 39 switched from placebo to inotersen (placebo-inotersen). The placebo-inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen-inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo-inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study.
conclusionInotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.