AveXis, Inc., a Novartis company, today announced that they have filed for FDA approval of AVXS-101, a gene therapy that replaces the survival motor neuron 1 (SMN1) gene, which is missing or mutated in individuals with SMA.

This first filing is for intravenous (IV) delivery of gene therapy. Based on typical practices, the expectation is that the FDA approval for IV delivery will closely match the IV clinical trial participants, who were SMA type I infants under nine months of age.

In addition, AveXis is currently testing intrathecal (IT) delivery of AVXS-101 in clinical trials. IT delivery would allow older and bigger patients to receive the therapy. Once these clinical trials are complete, AveXis will determine whether the data supports a separate BLA filing for IT delivery.

“We congratulate AveXis and Novartis on reaching this milestone,” said Kenneth Hobby, President of Cure SMA. “The IV clinical trial data shows that a one-time dose of gene therapy has the potential for a transformative impact on this life-threatening disease. We look forward to a rapid approval by the FDA, and then future positive results from the ongoing intrathecal clinical trials.”

Next Steps

The filing that AveXis announced today is called a Biologics License Application, or BLA. The FDA will first review the application to make sure it is complete. After that review, the FDA will then evaluate the application to determine that AVXS-101 is safe and effective when given via IV delivery.

A final decision is expected in the first half of 2019.

Cure SMA Supports Multiple Gene Therapy Approaches

Beginning in 2010, Cure SMA made a series of grants to Nationwide Children’s Hospital to study gene therapy, also called gene transfer. Spinal muscular atrophy (SMA) is caused by a mutation in the survival motor neuron 1 gene (SMN1). Because of this mutation, the individual does not produce enough survival motor neuron (SMN) protein.

Gene transfer may increase SMN levels by using a virus, called a vector, to deliver the SMN1 gene to affected cells. Adeno-associated virus serotype 9 (AAV9) has the unique ability to cross the blood brain barrier and the Blood-Cerebrospinal Fluid Barrier (CSF).

Currently, two approaches are being studied: an injection into a vein, known as IV delivery, and injection directly into the CSF, a process known as IT delivery. The IV delivery approach is currently under review for approval by the FDA.

IT delivery of gene therapy has shown promise for reducing the amount of drug required for larger and older patients. This could eventually make the treatment accessible to a wider population. IT delivery of gene therapy is currently being tested in clinical trials.

For More Information

Read a community statement from AveXis on this FDA filing.