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2328-95037122020DecAnnals of clinical and translational neurologyAnn Clin Transl NeurolViltolarsen in Japanese Duchenne muscular dystrophy patients: A phase 1/2 study.239324082393-240810.1002/acn3.51235The novel morpholino antisense oligonucleotide viltolarsen targets exon 53 of the dystrophin gene, and could be an effective treatment for patients with Duchenne muscular dystrophy (DMD). We investigated viltolarsen's ability to induce dystrophin expression and examined its safety in DMD patients.In this open-label, multicenter, parallel-group, phase 1/2, exploratory study, 16 ambulant and nonambulant males aged 5-12 years with DMD received viltolarsen 40 or 80 mg/kg/week via intravenous infusion for 24 weeks. Primary endpoints were dystrophin expression and exon 53 skipping levels.In western blot analysis, mean changes in dystrophin expression (% normal) from baseline to Weeks 12 and 24 were - 1.21 (P = 0.5136) and 1.46 (P = 0.1636), respectively, in the 40 mg/kg group, and 0.76 (P = 0.2367) and 4.81 (P = 0.0536), respectively, in the 80 mg/kg group. The increase in mean dystrophin level at Weeks 12 and 24 was significant in the 80 mg/kg group (2.78%; P = 0.0364). Patients receiving 80 mg/kg showed a higher mean exon 53 skipping level (42.4%) than those receiving 40 mg/kg (21.8%). All adverse events were judged to be mild or moderate in intensity and none led to study discontinuation.Treatment with viltolarsen 40 or 80 mg/kg elicited an increasing trend in dystrophin expression and exon 53 skipping levels, and was safe and well tolerated. The decline in motor function appeared less marked in patients with higher dystrophin levels; this may warrant further investigation. This study supports the potential clinical benefit of viltolarsen.© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.KomakiHirofumiH0000-0002-0659-1417Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.TakeshimaYasuhiroYDepartment of Pediatrics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.MatsumuraTsuyoshiTDepartment of Neurology, National Hospital Organization Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.OzasaShiroSDepartment of Pediatrics, Kumamoto University Hospital, Kumamoto, Kumamoto, Japan.FunatoMichinoriMDepartment of Pediatrics, National Hospital Organization Nagara Medical Center, Gifu, Japan.TakeshitaEriEDepartment of Child Neurology, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan.IwataYasuyukiYDepartment of Rehabilitation, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan.YajimaHiroyukiHDepartment of Rehabilitation, National Center of Neurology and Psychiatry, National Center Hospital, Kodaira, Tokyo, Japan.EgawaYoichiYGlobal Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan.ToramotoTakuyaTGlobal Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan.TajimaMasayaMGlobal Clinical Development Department, Nippon Shinyaku Co., Ltd., Kyoto, Kyoto, Japan.TakedaShinichiSNational Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.engClinical Trial, Phase IClinical Trial, Phase IIJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov't20201207
United StatesAnn Clin Transl Neurol1016232782328-95030Dystrophin0OligonucleotidesSXA7YP6EKXviltolarsenIMChildChild, PreschoolDystrophindrug effectsgeneticsmetabolismHumansJapanMaleMuscular Dystrophy, Duchennedrug therapygeneticsmetabolismphysiopathologyOligonucleotidesadministration & dosageadverse effectspharmacokineticspharmacologyOutcome Assessment, Health CareH.K. has received grants from Taiho, Pfizer Japan, Nippon Shinyaku, Daiichi Sankyo, Chugai, PTC Therapeutics; and personal fees from Sarepta Therapeutics. Y.T. has received grants from Nippon Shinyaku; and personal fees from Daiichi Sankyo and Biogen. T.M. has received grants from Nippon Shinyaku. S.O. has received grants from Nippon Shinyaku, Biogen, and PTC Therapeutics. M.F. has received grants from Nippon Shinyaku and Taiho. E.T. has received grants from Taiho, Nippon Shinyaku, Daiichi Sankyo, and Takeda; and personal fees from Pfizer Japan. 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