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FDA Orphan Drug Designation: Gene Therapy For Spinal Muscular Atrophy

October 7, 2014




I – Introduction

AveXis, a synthetic biology platform Dallas-based company formed in July 2013, announces on October 2nd, that the FDA grants Orphan Drug Designation (ODD) to the company’s gene therapy product, scAAV9.CB.SMN (called chariSMA), for the treatment of Spinal Muscular Atrophy (SMA). chariSMA is developed at Nationwide Children’s Hospital (Columbus, Ohio) and licensed to AveXis for development and commercialization.

II – SMA Facts

•   Genetic neuromuscular disease

•   Characterized by muscle atrophy and weakness

•   Leading genetic cause of infant mortality

•   Autosomal recessive disease (inherited from BOTH parents) caused by a missing or defective Survival Motor Neuron (SMN) gene

•   Affects 25,000 – 50,000 children and adults in the US, Europe, and Japan.

III- What is chariSMA Gene Therapy?

“The chariSMATM approach is a gene transfer therapy to introduce fully functioning copies of a SMN gene, intended to supplement the body’s production of SMN protein. chariSMATM (scAAV9.CB.SMN) is an adeno-associated viral vector carrying the SMN gene. After IV administration, the viral vector crosses the blood-brain-barrier to deliver the SMN gene into motor neurons of the spinal cord. The newly introduced SMN gene exists in an episomal or extrachromosomal form, meaning that the new gene will not integrate into the genome of the cell. The cell machinery will then continually produce SMN protein from the new copies of the SMN gene. The chariSMATM approach is much like introducing a “third gene” for producing SMN protein.” (Reference ChariSMA Quick Sheet)

AveXis is currently recruiting for a Phase I gene transfer clinical trial using chariSMA in SMA Type 1 infants at Nationwide Children’s Hospital. The Hospital receives IND approval and Fast Track designation from the FDA in September 2013.

The Phase I trial is sponsored by The Sophia’s Cure Foundation and AveXis. The Gaynor family (New York City) formed The Sophia’s Cure Foundation, a non-profit 501(c)3 public charity, after their daughter Sophia is diagnosed in 2009 with SMA. The mission of the foundation is to help fund clinical research to find a cure for SMA and to provide support for SMA families. In June 2014, the first patient in the “Gene Transfer Clinical Trial for SMA Type 1” is enrolled and dosed by Nationwide Children’s Hospital.

The challenge with gene therapy for SMA, is to find a mechanism for delivering the genetic material to the spinal cord – to be able to effectively and safely carry the genetic material across the blood brain barrier. A recent development in gene therapy is a virus called the AAV9, which can reach motor neurons effectively.

No gene therapy has ever been approved for sale in the United States. In Europe, the EMA (European Medicines Agency), has given regulatory approval to UniQure, to sell its gene therapy, Glybera, for the treatment of the rare disease, Lipoprotein Lipase Deficiency (LPLD). UniQure’s gene therapy receives FDA orphan drug designation in May 2007.

IV – FDA Rare Pediatric Disease Priority Review Voucher (PRV)

In AveXis’ October 2nd Press Release announcing the FDA ODD, there is mention of the FDA Rare Pediatric Disease Priority Review Voucher (PRV):

” … AveXis could qualify for a Rare Pediatric Disease Priority Review Voucher (PRV). The priority review voucher is an expedited review granted by the Food and Drug Administration (FDA) to the developer of a treatment for neglected diseases.”

V – AveXis Company Name Derivation

According to AveXis’ website, the name AveXis has an interesting derivation:

•   Av = Adeno-Associated Virus (AAV)

•   ve = vector

•    X  = DNA helix

•    is = Isis (goddess of children, nature and magic).

VI – FDA ODD Database Record For SMA Gene Therapy

Generic Name: Adeno-associated virus serotype 9 expressing the human Survival Motor Neuron gene
Trade Name: n/a
Date Designated: 09-30-2014
Orphan Designation: Spinal Muscular Atrophy
Orphan Designation Status: Designated
FDA Orphan Approval Status: Not FDA Approved for Orphan Indication
Sponsor: AveXis, Inc. One Energy Square Suite 604 Dallas, TX 75206 The sponsor address listed is the last reported by the sponsor to OOPD.


Please Note: “DNA Repair” courtesy of Tom Ellenberger, Washington University School of Medicine in St. Louis. [Public domain] | Wikimedia Commons.

Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

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