Novartis (Avexis) AVXS-101

SMA is caused by mutation of the SMN1 gene. Researchers think that we may be able to treat SMA by replacing this faulty gene.

A type of treatment known as gene therapy, or gene transfer, is thought to be a viable option for restoring the SMN protein that is lacking in SMA patients. As well as replacing SMN1, gene transfer, targeting other important genes, could also be used to provide additional protection to motor neurons, the main cells affected by SMA.

The Nationwide Children Hospital Research Institute received FDA’s fast track status for a gene therapy product, scAAV9,  in October 2013 and Orphan Drug status in October 2014. Regenx Biosciences and AveXis entered into an exclusive license agreement for the development of this gene therapy product on 1st April 2014.

In May 2018, Avexis was acquired by Novartis.

Ongoing gene therapy trial for SMA

Avexis AVXS-101

Pivotal Trial (September 2017)

AveXis announced in September 2017 that the U.S. Food and Drug Administration (FDA), based on review of data submitted, including the potency assay, the company could initiate its planned pivotal trial of AVXS-101 for patients with SMA Type 1 using the intravenous (IV) formulation produced by the company’s Good Manufacturing Practice (GMP) commercial manufacturing process.

The company plans to initiate this trial immediately.

Phase 1 Trial results (March 2017)

The completed trial data indicated that AVXS-101 appears to be safe and well tolerated by the young SMA Type 1 patients being treated. Importantly, it also appeared to result in improved and sustained muscle function.

The trial included two different treatment strategies:

The following highlights from the trial were reported by AveXis, which are accurate as of January 20th, 2017:

To continue AVXS-101 development, AveXis announced that they are to initiate two pivotal trials of their gene therapy:

These new trials will enrol patients with SMA Type 1 and are “single-arm”, meaning that there is no patient group receiving a placebo; rather, motor milestone achievements of patients receiving AVXS-101 will be compared to natural history information from untreated SMA patients.

More information

Clinical Trials Registry
AveXis website
Pivotal Trial Press Announcement


In December 2017, Avexis was granted authorisation to start Phase 1 clinical trial of AVXS-101 for patients with SMA Type 2 by the FDA in the U.S., based on review of data submitted. The company plans to initiate this trial immediately.

The open-label, dose-comparison, multi-center Phase 1 trial named STRONG, is designed to evaluate the safety, optimal dosing and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, using a one-time IT route of administration. The trial will enroll 27 infants and children with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2 genetic modifier, who are able to sit but have no historical or current ability to stand or walk.

Two dosage strengths will be evaluated and patients will be stratified into two age groups:

patients less than 24 months
patients at least 24 months but less than 60 months.
There will be at least a four-week interval between the dosing of the first three patients for each dose being studied and based on the available safety data, a decision will be made whether to proceed.

Cohort 1 (Dose A) will receive a dose of 6.0 x 1013 vg of AVXS-101 and enroll three patients less than 24 months of age. If safety is established according to the Data Safety Monitoring Board (DSMB), the study will proceed to Cohort 2.
Cohort 2 (Dose B) will receive a dose of 1.2 X 1014 vg of AVXS-101 and enroll three patients less than 60 months of age.
If safety is established, an additional 21 patients will be enrolled until there are a total of 12 patients less than 24 months and 12 patients at least 24 months but less than 60 months of age, who have received Dose B.


This is a phase 3, open-label, single-arm study of a single, one-time dose of AVXS-101 in patients with SMA who meet enrollment criteria and are genetically defined by bi-allelic deletion of SMN1 with 2, 3, or 4 copies of SMN2. Patients with SMN1 point mutations or the SMN2 gene modifier mutation (c.859G>C) may enroll but will not be included in the efficacy analysis sets.

The study will enroll at least 15 patients with 2 copies of SMN2 that meet the Intent To Treat (ITT) criteria, at least twelve (12) patients with 3 copies of SMN2 that meet the ITT criteria and at least 17 patients with 4 copies of SMN2 that meet the ITT criteria. Patients in all three cohorts must be ≤6 weeks of age at the time of gene replacement therapy (Day 1).

SPR1NT Community update – May 2018

For more information