ZOLGENSMA

Proper Name: Onasemnogene Abeparvovec-xioi

ZOLGENSMA is a suspension of an adeno-associated viral vector-based gene therapy for intravenous infusion. It is a recombinant self-complementary AAV9 containing a transgene encoding the human survival motor neuron (SMN) protein, under the control of a cytomegalovirus enhancer/chicken-β-actin hybrid promoter.

Advisory Board:

No advisory committee meeting was held because initial review of information submitted in the BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.

Indications: For the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

Key Regulatory Milestones:

24/05/2019	US FDA Approval
05/18/2020	EU approval
12/16/2020	Health Canada approval
03/19/2020	Japan Approval

Manufacturing Platform:

PARAMETER	DATA
Manufacturer	AveXis, Inc
Transgene	Survival motor neuron gene (SMN1)
Indication	For the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Virus and Serotype	AAV serotype 9 (AAV9)
Cell Substrate	Human embryonic kidney cells (HEK293)
Manufacturing platform	Plasmid triple transfection
Dose in vial/final container	2.0 10e13 vector genomes / mL
Dose / patient	1.1 10e13 vector genomes / kg

SUPPORTING CLINICAL TRIALS

NCT	TRIAL PHASE	SUBJECTS ENROLLED	STUDY TITLE	COUNTRIES
Completed Phase 1 trial
NCT03421977	1	13	Long-term follow-up study for patients from AVXS-101-CL-101	United States
Ongoing trials
NCT03306277	3	22	Gene replacement therapy clinical trial for participants with Spinal Muscular Atrophy type 1	United States
NCT03505099	3	30	Pre-symptomatic study of intravenous onasemnogene abeparvovec-xioi in Spinal Muscular Atrophy (SMA) for patients with multiple copies of SMN2	United States, Italy, Australia, Belgium, Israel, Japan, Spain, Canada, Taiwan, Germany, Korea, Republic of, United Kingdom
NCT03461289	3	33	Single-dose gene replacement therapy clinical trial for patients with spinal muscular atrophy type 1	Belgium, France, Italy, United Kingdom

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