Gene Transfer Clinical Trial for Spinal Muscular Atrophy Type 1

Summary

The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of AVXS-101 as a treatment of spinal muscular atrophy Type 1 (SMN1).

Timeline

Start

2014-05-05

Primary completion

2017-12-15

Completion

2017-12-15

Outcome

Met primary endpoint

release “In a clinical study, AVXS-101 showed life-saving efficacy, with all 15 infants treated event free at 20 months” novartis.com ↗

release “In the START trial, patients treated with Zolgensma achieved motor milestones never seen in the natural history of the disease” novartis.com ↗

Publications

• Background Bevan AK, Duque S, Foust KD, Morales PR, Braun L, Schmelzer L, Chan CM, McCrate M, Chicoine LG, Coley BD, Porensky PN, Kolb SJ, Mendell JR, Burghes AH, Kaspar BK. Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther. 2011 Nov;19(11):1971-80. doi: 10.1038/mt.2011.157. Epub 2011 Aug 2.
• Background Bevan AK, Hutchinson KR, Foust KD, Braun L, McGovern VL, Schmelzer L, Ward JG, Petruska JC, Lucchesi PA, Burghes AH, Kaspar BK. Early heart failure in the SMNDelta7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery. Hum Mol Genet. 2010 Oct 15;19(20):3895-905. doi: 10.1093/hmg/ddq300. Epub 2010 Jul 16.
• Background Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, Le TT, Morales PR, Rich MM, Burghes AH, Kaspar BK. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010 Mar;28(3):271-4. doi: 10.1038/nbt.1610. Epub 2010 Feb 28.
• Background Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65. doi: 10.1038/nbt.1515. Epub 2008 Dec 21.
• Waldrop MA, Escudero RB, Yang L, Camarata RA, Branic EC, Mehl L, Ilic A, Connolly AM. Safety and efficacy of intravenous onasemnogene abeparvovec gene therapy in patients with spinal muscular atrophy type 1: interim analysis from LT-001, a long-term follow-up study of patients from the START study. EClinicalMedicine. 2026 Apr 13;94:103867. doi: 10.1016/j.eclinm.2026.103867. eCollection 2026 Apr.
• Day JW, Mendell JR, Mercuri E, Finkel RS, Strauss KA, Kleyn A, Tauscher-Wisniewski S, Tukov FF, Reyna SP, Chand DH. Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Drug Saf. 2021 Oct;44(10):1109-1119. doi: 10.1007/s40264-021-01107-6. Epub 2021 Aug 12.
• Lowes LP, Alfano LN, Arnold WD, Shell R, Prior TW, McColly M, Lehman KJ, Church K, Sproule DM, Nagendran S, Menier M, Feltner DE, Wells C, Kissel JT, Al-Zaidy S, Mendell J. Impact of Age and Motor Function in a Phase 1/2A Study of Infants With SMA Type 1 Receiving Single-Dose Gene Replacement Therapy. Pediatr Neurol. 2019 Sep;98:39-45. doi: 10.1016/j.pediatrneurol.2019.05.005. Epub 2019 May 13.
• Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guerin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM. Survival, Motor Function, and Motor Milestones: Comparison of AVXS-101 Relative to Nusinersen for the Treatment of Infants with Spinal Muscular Atrophy Type 1. Adv Ther. 2019 May;36(5):1164-1176. doi: 10.1007/s12325-019-00923-8. Epub 2019 Mar 16.
• Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, Church K, Lehman K, Sproule DM, Dabbous O, Maru B, Berry K, Arnold WD, Kissel JT, Mendell JR, Shell R. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019 Feb;54(2):179-185. doi: 10.1002/ppul.24203. Epub 2018 Dec 12.
• Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K, Kissel JT, Nagendran S, L'Italien J, Sproule DM, Wells C, Cardenas JA, Heitzer MD, Kaspar A, Corcoran S, Braun L, Likhite S, Miranda C, Meyer K, Foust KD, Burghes AHM, Kaspar BK. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017 Nov 2;377(18):1713-1722. doi: 10.1056/NEJMoa1706198.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	AVXS-101	Gene therapy (AAV / viral vector)	2 vg/kg	Intravenous
Subject	AVXS-101	Gene therapy (AAV / viral vector)	6.7 vg/kg	Intravenous

Indications