Rare Diseases Report 2022

Novel gene-based therapies for neuromuscular diseases


 

70. Biogen. A study to assess the efficacy, safety, tolerability, and pharmacokinetics of multiple doses of ISIS 396443 delivered intrathecally to patients with infantile-onset spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT01839656. Updated Feb 17, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT01839656.

71. Biogen. An open-label extension study for patients with spinal muscular atrophy who previously participated in investigational studies of ISIS 396443. ClinicalTrials.gov Identifier: NCT02594124. Updated Nov 15, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02594124.

72. Biogen. Escalating dose and randomized, controlled study of nusinersen (BIIB058) in participants with spinal muscular atrophy. ClinicalTri-als.gov Identifier: NCT04089566. Updated Feb 24, 2022. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04089566.

73. National Center for Advancing Translational Sciences. Duchenne muscular dystrophy. Genetic and Rare Diseases Information Center. Up-dated Nov 2, 2020. Accessed Mar 1, 2022. https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy.

74. Matsuo M. Antisense oligonucleotide-mediated exon-skipping therapies: Precision medicine spreading from Duchenne muscular dystrophy. JMA J. 2021 Jul 15;4(3):232-40. doi:10.31662/jmaj.2021-0019.

75. FDA approves drug to treat Duchenne muscular dystrophy. U.S. Food and Drug Administration. News release. Feb 9, 2017. Accessed Mar 1, 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-drug-treat-duchenne-muscular-dystrophy.74.

76. Duan D. Dystrophin gene replacement and gene repair therapy for Duchenne muscular dystrophy in 2016: An interview. Hum Gene Ther Clin Dev. 2016 Mar;27(1):9-18. doi:10.1089/humc.2016.001.

77. EXONDYS 51®. Parent Project Muscular Dystrophy. Accessed August 21, 2022. https://www.parentprojectmd.org/drug-development-pipeline/exondys-51/

78. Sarepta Therapeutics, Inc. A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Efficacy, Safety, Tolerability and Pharmacoki-netics Study of AVI-4658(Eteplirsen),in the Treatment of Ambulant Subjects With Duchenne Muscular Dystrophy. clinicaltrials.gov; 2020. Ac-cessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT01396239

79. Sarepta Therapeutics, Inc. Clinical Study to Assess the Safety Fo AVI-4658 in Subjects With Duchenne Muscular Dystrophy Due to a Frame-Shift Mutation Amenable to Correction by Skipping Exon 51. clinicaltrials.gov; 2015. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/study/NCT00844597

80. Sarepta Therapeutics, Inc. A 2-part, randomized, double-blind, placebo-controlled, dose-titration, safety, tolerability, and pharmacokinetics study (Part 1) followed by an open-label efficacy and safety evaluation (Part 2) of SRP-4053 in patients with Duchenne muscular dystrophy amenable to exon 53 skipping. ClinicalTrials.gov Identifier: NCT02310906. Updated Oct 19, 2020. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/results/NCT02310906.

81. Commissioner O of the. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. FDA. Published March 24, 2020. Accessed August 21, 2022. hDuchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment. clinicaltrials.gov; 2022. Accessed Au-gust 18, 2022. https://clinicaltrials.gov/ct2/show/NCT04004065

109. National Center of Neurology and Psychiatry, Japan. Exploratory study of NS-065/NCNP-01 in Duchenne muscular dystrophy. ClinicalTri-als.gov Identifier: NCT02081625; Updated Feb 26, 2020. Accessed Mar 2, 2022. https://clinicaltrialsttps://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-drug-duchenne-muscular- dys-trophy

82. Duchenne Drug Development Pipeline. Parent Project Muscular Dystrophy. Accessed August 21, 2022. https://www.parentprojectmd.org/duchenne-drug-development-pipeline/

83. Sarepta Therapeutics Provides Update on SRP-5051 for the Treatment of Duchenne Muscular Dystrophy | Sarepta Therapeutics, Inc. Ac-cessed August 22, 2022. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics- pro-vides-update-srp-5051-treatment-duchenne

84. Sarepta Therapeutics, Inc. An Open-Label Extension Study for Patients With Duchenne Muscular Dystrophy Who Participated in Studies of SRP-5051. clinicaltrials.gov; 2021. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03675126

85. VYONDYS 53. Prescribing information. Sarepta Therapeutics Inc.; 2019. Accessed Mar 2, 2022. http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211970s000lbl.pdf.

86. NS Pharma Inc. Long-term use of viltolarsen in boys with Duchenne muscular dystrophy in clinical practice (VILT-502). ClinicalTrials.gov Identifier: NCT04687020. Updated Nov 22, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04687020.

87. VILTEPSO. Prescribing information. NS Pharma; 2020. Accessed Mar 2, 2022. http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212154s000lbl.pdf.

88. FDA approves targeted treatment for rare Duchenne muscular dystrophy mutation. U.S. Food and Drug Administration. News release. Feb 25, 2021. Accessed Mar 1, 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-dystrophy-mutation-0.

89. Sarepta Therapeutics Inc. A double-blind, placebo-controlled, multi-center study with an open-label extension to evaluate the efficacy and safety of SRP-4045 and SRP-4053 in patients with Duchenne muscular dystrophy. Clinicaltrials.gov Identifier: NCT02500381. Updated Aug 19, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02500381.

90. AMONDYS 45. Prescribing information. Sarepta Therapeutics Inc.; 2021. Accessed Feb 22, 2022. http://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213026lbl.pdf.

91. Finkel RS et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dys-trophy. PLoS ONE. 2013;8(12):e81302. doi:10.1371/journal.pone.0081302.

92. PTC Therapeutics. A phase 2 study of PTC124 as an oral treatment for nonsense-mutation-mediated Duchenne muscular dystrophy. Clini-calTrials.gov Identifier: NCT00264888. Updated Jan 14, 2009. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT00264888.

93. PTC Therapeutics. A phase 2B efficacy and safety study of PTC124 in subjects with nonsense-mutation-mediated Duchenne and Becker muscular dystrophy. ClinicalTrials.gov Identifier: NCT00592553. Updated Apr 7, 2020. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT00592553.

94. PTC Therapeutics. A phase 3 efficacy and safety study of ataluren in patients with nonsense mutation dystrophinopathy. ClinicalTrials.gov Identifier: NCT01826487. Updated Aug 4, 2020. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT01826487.

95. Bushby K et al; PTC124-GD-007-DMD Study Group. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014 Oct;50(4):477-87. doi:10.1002/mus.24332.

96. Solid Biosciences LLC. A randomized, controlled, open-label, single-ascending dose, phase I/II study to investigate the safety and tolerabil-ity, and efficacy of intravenous SGT-001 in male adolescents and children with Duchenne muscular dystrophy. ClinicalTrials.gov Identifier: NCT03368742. Updated Aug 24, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03368742.

97. Solid Biosciences reports 1.5-year data from patients in the ongoing IGNITE DMD phase I/II clinical trial of SGT-001. Press release. Solid Biosciences. Sep 27, 2021. Accessed Mar 2, 2022. http://www.solidbio.com/about/media/press-releases/solid-biosciences-reports-1-5-year-data-from-patients-in-the-ongoing-ignite-dmd-phase-i-ii-clinical-trial-of-sgt-001.

98. Potter RA et al. Dose-escalation study of systemically delivered rAAVrh74.MHCK7.microdystrophin in the mdx mouse model of Duchenne muscular dystrophy. Hum Gene Ther. 2021 Apr;32(7-8):375-89. doi:10.1089/hum.2019.255.

99. Sarepta Therapeutics, Inc. A Phase 3 Multinational, Randomized, Double-Blind, Placebo- Controlled Systemic Gene Delivery Study to Evaluate the Safety and Efficacy of SRP-9001 in Patients With Duchenne Muscular Dystrophy (EMBARK). clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT05096221

100. Pfizer. A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF 06939926 FOR THE TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY. clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT04281485

101. Pfizer. A phase 1B multicenter open-label, single ascending dose study to evaluate the safety and tolerability of PF-06939926 in ambula-tory and non-ambulatory subjects with Duchenne muscular dystrophy. ClinicalTrials.gov Identifier: NCT03362502. Updated Mar 2, 2022. Ac-cessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03362502.

102. MS MW. Phase 3 CIFFREO DMD Gene Therapy Trial Slated to Begin in June in US. Accessed August 21, 2022. https://musculardystrophynews.com/news/phase-3-trial-of-pfizers-gene-therapy- expected-to-open-in-us-in-june/

103. SRP-9001. Parent Project Muscular Dystrophy. Accessed August 22, 2022. https://www.parentprojectmd.org/drug-development-pipeline/srp-9001-micro-dystrophin-gene- transfer/

104. Sarepta Therapeutics’ Investigational Gene Therapy SRP-9001 for Duchenne Muscular Dystrophy Demonstrates Significant Functional Improvements Across Multiple Studies | Sarepta Therapeutics, Inc. Accessed August 22, 2022. https://investorrelations.sarepta.com/news-releases/news-release- details/sarepta-therapeutics-investigational-gene-therapy-srp-9001

105. Sarepta Therapeutics, Inc. An Open-Label Safety, Tolerability, and Efficacy Study of Eteplirsen in Patients With Duchenne Muscular Dys-trophy Who Have Completed Study 4658-102.clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03985878

106. Sarepta Therapeutics, Inc. An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Mus-cular Dystrophy Amenable to Exon 51 Skipping. clinicaltrials.gov; 2021. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03218995

107.Sarepta Therapeutics, Inc. A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of a High Dose of Eteplirsen, Preceded by an Open-Label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping. clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03992430

108. Sarepta Therapeutics, Inc. A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Ex-pansion, in Patients With .gov/ct2/show/NCT02081625.

110. NS Pharma Inc. A phase II, dose finding study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of NS-065/NCNP-01 in boys with Duchenne muscular dystrophy (DMD). ClinicalTrials.gov Identifier: NCT02740972. Updated Dec 7, 2021. Ac-cessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT02740972.

111. NS Pharma Inc. A phase II, open-label, extension study to assess the safety and efficacy of NS-065/NCNP-01 in boys with Duchenne muscular dystrophy (DMD). ClinicalTrials.gov Identifier: NCT03167255. Updated Nov 24, 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03167255.

112. NS Pharma Inc. A phase 2 open label study to assess the safety, tolerability, and efficacy of viltolarsen in ambulant and non-ambulant boys with Duchenne muscular dystrophy (DMD) compared with natural history controls. ClinicalTrials.gov Identifier: NCT04956289. Updated Feb 1, 2022. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT04956289.

113. NS Pharma Inc. A phase 3 randomized, double-blind, placebo-controlled, multi-center study to assess the efficacy and safety of viltolarsen in ambulant boys with Duchenne muscular dystrophy (DMD). ClinicalTrials.gov Identifier: NCT04060199. Updated Nov 16, 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT04060199.

114. NS Pharma Inc. A phase 3, multi-center, open-label extension study to assess the safety and efficacy of viltolarsen in ambulant boys with Duchenne muscular dystrophy (DMD). ClinicalTrials.gov Identifier: NCT04768062. Updated Nov 16, 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT04768062.

115. Sarepta Therapeutics Inc. A randomized, double-blind, placebo-controlled, dose-titration, safety, tolerability, and pharmacokinetics study followed by an open-label safety and efficacy evaluation of SRP-4045 in advanced-stage patients with Duchenne muscular dystrophy amena-ble to exon 45 skipping. ClinicalTrials.gov Identifier: NCT02530905. Updated May 17, 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT02530905.

116. Sarepta Therapeutics Inc. Long-term, open-label extension study for patients with Duchenne muscular dystrophy enrolled in clinical trials evaluating casimersen or golodirsen. ClinicalTrials.gov Identifier: NCT03532542. Updated Dec 20, 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03532542.

117. PTC Therapeutics. A phase 2 study of the safety, pharmacokinetics, and pharmacodynamics of ataluren (PTC124®) in patients aged ≥2 to <5 years old with nonsense mutation dystrophinopathy. ClinicalTrials.gov Identifier: NCT02819557. Updated Aug 28, 2020. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT02819557.

118. PTC Therapeutics. Phase 2, non-interventional, clinical study to assess dystrophin levels in subjects with nonsense mutation Duchenne muscular dystrophy who have been treated with ataluren for ≥ 9 months. ClinicalTrials.gov Identifier: NCT03796637. Updated Apr 10, 2020. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03796637.

119. PTC Therapeutics. An Open-Label Study Evaluating the Safety and Pharmacokinetics of Ataluren in Children From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy. clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT04336826 120. PTC Therapeutics. An open-label study for previously treated ataluren (PTC124®) pa-tients with nonsense mutation dystrophinopathy. ClinicalTrials.gov Identifier: NCT01557400. Updated Nov 25, 2020. Accessed Feb 21, 2022. https://clinicaltrials.gov/ct2/show/NCT01557400.

121. PTC Therapeutics. An open-label, safety study for ataluren (PTC124) patients with nonsense mutation dystrophinopathy. ClinicalTrials.gov Identifier: NCT01247207. Updated Feb 16, 2022. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT01247207.

122. PTC Therapeutics. A phase 3, randomized, double-blind, placebo-controlled efficacy and safety study of ataluren in patients with non-sense mutation Duchenne muscular dystrophy and open-label extension. ClinicalTrials.gov Identifier: NCT03179631. Updated Feb 8, 2022. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03179631.

123. Sarepta Therapeutics, Inc. An Open-Label, Systemic Gene Delivery Study Using Commercial Process Material to Evaluate the Safety of and Expression From SRP-9001 in Subjects With Duchenne Muscular Dystrophy (ENDEAVOR). clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT04626674

124. Sarepta Therapeutics, Inc. Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using RAA-Vrh74.MHCK7.Micro-Dystrophin (MicroDys-IV-001). clinicaltrials.gov; 2022. Accessed August 18, 2022. https://clinicaltrials.gov/ct2/show/NCT03375164

125. Sarepta Therapeutics Inc. A multicenter, randomized, double-blind, placebo-controlled trial for Duchenne muscular dystrophy using SRP-9001. ClinicalTrials.gov Identifier: NCT03769116. Updated Dec 2021. Accessed Mar 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03769116.

126. Hoffmann-La Roche. A Two-Part, Seamless, Multi-Center, Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Ambulant Pa-tients With Spinal Muscular Atrophy. clinicaltrials.gov; 2022. Accessed September 1, 2022. https://clinicaltrials.gov/ct2/show/NCT05115110

Pages

Recommended Reading

Inebilizumab beneficial across genotypes in NMOSD
MDedge Neurology
Tofersen linked to slow, positive effects in ALS
MDedge Neurology
FDA unveils 5-year plan for ALS and other neurodegenerative diseases
MDedge Neurology
First-ever Huntington staging system may jump-start drug development for early-stage disease
MDedge Neurology
Two deaths from liver failure linked to spinal muscular atrophy drug
MDedge Neurology
Polio: The unwanted sequel
MDedge Neurology
CDC warns of enterovirus strain linked to polio-like condition
MDedge Neurology
Ketamine promising for rare condition linked to autism
MDedge Neurology
ALS drug gets FDA panel thumbs-up after rare second look
MDedge Neurology
Myasthenia gravis: Finding strength in treatment options
MDedge Neurology