Rare Diseases Report 2022

Novel gene-based therapies for neuromuscular diseases


 

37. Scoto M et al. Genetic therapies for inherited neuromuscular disorders. Lancet Child Adolesc Health. 2018 Aug;2(8):600-9. doi:10.1016/S2352-4642(18)30140-8.

38. Abreu NJ, Waldrop MA. Overview of gene therapy in spinal muscular atrophy and Duchenne muscular dystrophy. Pediatr Pulmonol. 2021 Apr;56(4):710-20. doi:10.1002/ppul.25055.

39. Brandsema J, Cappa R. Genetically targeted therapies for inherited neuromuscular disorders. Practical Neurology [Internet]. Jul/Aug 2021:69-73. Accessed Mar 1, 2022. https://practicalneurology.com/articles/2021-july-aug/genetically-targeted-therapies-for-inherited-neuromuscular-disorders/pdf.

40. Ojala KS et al. In search of a cure: The development of therapeutics to alter the progression of spinal muscular atrophy. Brain Sci. 2021;11(2):194. doi:10.3390/brainsci11020194.

41. McCall S. Cure SMA Releases Updated Drug Pipeline. Cure SMA. Published December 13, 2021. Accessed August 21, 2022. https://www.curesma.org/cure-sma-releases-updated-drug-pipeline- 2021/ 42. FDA approves first drug for spinal muscular atrophy. U.S. Food and Drug Administration. News release. Dec 23, 2016. Accessed Mar 1, 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-spinal-muscular-atrophy.43. Kirschner J. Postnatal gene therapy for neuromuscular diseases – Opportunities and limitations. J Perinat Med. 2021 Sep;49(8):1011-5. doi:10.1515/jpm-2021-0435.

43. Terryn J, Verfaillie CM, Van Damme P. Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities. Front Mol Neurosci. 2021;14. Accessed September 4, 2022. https://www.frontiersin.org/articles/10.3389/fnmol.2021.71303144.

44. Biogen. A phase 3, randomized, double-blind, sham-procedure controlled study to assess the clinical efficacy and safety of ISIS 396443 administered intrathecally in patients with later-onset spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT02292537. Updated Feb 17, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/study/NCT02292537.

45. Why Spinraza/later-onset studies. SPINRAZA® (nusinersen) [Internet]. Accessed Mar 1, 2022. www.spinraza.com/en_us/home/why-spinraza/later-onset-studies.html#scroll-tabs.

46. Biogen. A Phase 3, Randomized, Double-Blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients With Infantile- Onset Spinal Muscular Atrophy. clinicaltrials.gov; 2021. Accessed February 10, 2022. https://clinicaltrials.gov/ct2/show/results/NCT02193074

47. Early-onset SMA (Type 1) | SPINRAZA® (nusinersen). Accessed Mar 1, 2022. https://www.spinraza-hcp.com/en_us/home/why-spinraza/about-spinraza.html.

48. Finkel RS et al; ENDEAR Study Group. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377(18):1723-32. doi: 10.1056/NEJMoa1702752.

49. Biogen. An open-label study to assess the efficacy, safety, tolerability, and pharmacokinetics of multiple doses of ISIS 396443 delivered intrathecally to subjects with genetically diagnosed and presymptomatic spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT02386553. Updated Nov 18, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02386553.

50. De Vivo DC et al; NURTURE Study Group. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: In-terim efficacy and safety results from the phase 2 NURTURE study. Neuromuscul Disord. 2019 Nov;29(11):842-56. doi:10.1016/j.nmd.2019.09.007.

51. Why Spinraza/presymptomatic study. SPINRAZA® (nusinersen) [Internet]. Accessed Feb 22, 2022. www.spinraza.com/en_us/home/why-spinraza/presymptomatic-study.html#scroll-tabs.

52. FDA approves oral treatment for spinal muscular atrophy. U.S. Food and Drug Administration. News release. Aug 7, 2020. Accessed Mar 1, 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-oral-treatment-spinal-muscular-atrophy.

53. Hoffmann-La Roche. A two-part seamless, open-label, multicenter study to investigate the safety, tolerability, pharmacokinetics, pharmaco-dynamics and efficacy of risdiplam (RO7034067) in infants with type 1 spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT02913482. Updated Jan 21, 2022. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02913482.

54. Hoffmann-La Roche. A two-part seamless, multi-center randomized, placebo-controlled, double-blind study to investigate the safety, tolera-bility, pharmacokinetics, pharmacodynamics and efficacy of risdiplam (RO7034067) in type 2 and 3 spinal muscular atrophy patients. Clinical-Trials.gov Identifier: NCT02908685. Updated Dec 28, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02908685.

55. Genentech. Genentech’s risdiplam shows significant improvement in survival and motor milestones in infants with type 1 spinal muscular atrophy (SMA). Press release. Apr 27, 2020. Accessed Mar 1, 2022. http://www.gene.com/media/press-releases/14847/2020-04-27/genentechs-risdiplam-shows-significant-i

56. Hoffmann-La Roche. An open-label study to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of risdiplam (RO7034067) in adult and pediatric patients with spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT03032172. Updated Jan 27, 2022. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03032172.

57. Hoffmann-La Roche. An open-label study of risdiplam in infants with genetically diagnosed and presymptomatic spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT03779334. Updated Jan 27, 2022. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03779334.

58. McCall S. Update on Genentech/Roche Initiation of MANATEE Clinical Study. Cure SMA. Published October 20, 2021. Accessed August 20, 2022. https://www.curesma.org/update-on- genentech-roche-initiation-of-manatee-clinical-study/

59. Abati E, Manini A, Comi GP, Corti S. Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases. Cell Mol Life Sci. 2022;79(7):374. doi:10.1007/s00018-022-04408-w

60. FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality. U.S. Food and Drug Administration. News release. May 24, 2019. Accessed Mar 1, 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease.

61. Novartis Gene Therapies. Phase I gene transfer clinical trial for spinal muscular atrophy type 1 delivering AVXS-101. ClinicalTrials.gov Identifier: NCT02122952. Updated Jun 14, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT02122952.

62. Novartis Gene Therapies. Phase 3, open-label, single-arm, single-dose gene replacement therapy clinical trial for patients with spinal mus-cular atrophy type 1 with one or two SMN2 copies delivering AVXS-101 by intravenous infusion. ClinicalTrials.gov Identifier: NCT03306277. Updated Jun 14, 2021. Accessed Feb 21, 2022. https://clinicaltrials.gov/ct2/show/NCT03306277.

63. Mendell JR et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377(18):1713-22. doi:10.1056/NEJMoa1706198.

64. Symptomatic study results. ZOLGENSMA [Internet]. Updated Nov 2021. Accessed Mar 1, 2022. Error! Hyperlink reference not valid..

65. Novartis Gene Therapies. A global study of a single, one-time dose of AVXS-101 delivered to infants with genetically diagnosed and pre-symptomatic spinal muscular atrophy with multiple copies of SMN2. ClinicalTrials.gov Identifier: NCT03505099. Updated Jan 1, 2022. Ac-cessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03505099.

66. Chiu W et al. Current genetics and potential gene-targeting therapeutics for neuromuscular diseases. Int J Mol Sci. 2020 Dec;21(24):9589. doi:10.3390/ijms21249589.

67. Novartis Gene Therapies. A long-term follow-up study of patients in the clinical trials for spinal muscular atrophy receiving AVXS-101. Clini-calTrials.gov Identifier: NCT04042025. Updated Jun 9, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT04042025.

68. Novartis Gene Therapies. Phase 3, open-label, single-arm, single-dose gene replacement therapy clinical trial for patients with spinal mus-cular atrophy type 1 with one or two SMN2 copies delivering AVXS-101 by intravenous infusion. ClinicalTrials.gov Identifier: NCT0383718. Up-dated Jan 11, 2022. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT03837184.

69. Biogen. An open-label, dose escalation study to assess the safety, tolerability and dose-range finding of multiple doses of ISIS 396443 de-livered intrathecally to patients with spinal muscular atrophy. ClinicalTrials.gov Identifier: NCT01703988. Updated Apr 13, 2021. Accessed Mar 1, 2022. https://clinicaltrials.gov/ct2/show/NCT01703988.

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