Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

Thomas H.Brannagan; TeresaCoelho; Annabel K.WangMichael J.PolydefkisPeter J.DyckJohn L.BerkBrianDrachmanPeterGorevicCarolWhelanIsabelConcei??oViolainePlante-BordeneuveGiampaoloMerliniLauraObiciJosep Maria CampistolPlanaJosepGamezArnt V.KristenAnnaMazzeoLucaGentileArvindNarayanaKemiOlugemoPeterAquinoMerrill D.BensonMorieGertz

首页> 外文期刊>Journal of neurology >Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

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Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

机译：Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

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Abstract Background Hereditary 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.Methods Patients 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.Results In 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.Conclusion Inotersen treatment for > 3?years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed.

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《Journal of neurology》 |2022年第12期|6416-6427|共12页
作者
Thomas H.Brannagan; TeresaCoelho; Annabel K.WangMichael J.PolydefkisPeter J.DyckJohn L.BerkBrianDrachmanPeterGorevicCarolWhelanIsabelConcei??oViolainePlante-BordeneuveGiampaoloMerliniLauraObiciJosep Maria CampistolPlanaJosepGamezArnt V.KristenAnnaMazzeoLucaGentileArvindNarayanaKemiOlugemoPeterAquinoMerrill D.BensonMorieGertz;
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作者单位

Neurology and General Internal Medicine,Mayo Clinic;

Department of Neurology,Columbia University Medical Center;

Centro Hospitalar Universitário do PortoNeuromuscular Diagnostic Laboratory,University of CaliforniaDepartment of Neurology,Johns Hopkins UniversityAmyloid Clinic, Boston UniversityCardiovascular Medicine,Penn Presbyterian Medical CenterDepartment of Rheumatology,Mount Sinai Medical CenterCardiology, National Amyloidosis Centre, Royal Free HospitalDepartment of Neurology,CHULN, Hospital Santa Maria and Faculdade de Medicina, Universidade deCHU Henri MondorAmyloidosis Research and Treatment Center,IRCCS Fondazione Policlinico San Matteo, University ofHospital Clinic, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i SunyerNeurology Department,GMA Clinic, Autonomous University of Barcelona and European Reference NetworkAmyloidosis Center,Heidelberg University HospitalDepartment of Clinical and Experimental Medicine,University of MessinaAkcea TherapeuticsDepartment of Pathology and Laboratory Medicine,Indiana University School of Medicine;

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正文语种英语
中图分类神经病学;
关键词
Clinical trial; Familial amyloid polyneuropathy; Inotersen; Hereditary transthyretin amyloidosis; Peripheral neuropathies; Polyneuropathy;

Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

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