Our proprietary gene therapy candidate, AVXS-101, has been granted Orphan Drug Designation for the treatment of all types of spinal muscular atrophy (SMA) and Breakthrough Therapy Designation, as well as Fast Track Designation, for the treatment of SMA Type 1—one of the most life-threatening neurological genetic disorders.

Decoding SMA

Spinal muscular atrophy (SMA) is a severe neuromuscular disease caused by a genetic defect in the SMN1 gene – leading to the loss of motor neurons and resulting in progressive muscle weakness and paralysis. SMA is divided into sub-categories – SMA Types 1, 2, 3, and 4 – based on disease onset and severity, which generally correlate to survival motor neuron (SMN) protein levels.

Our primary focus is to develop gene therapies for SMA, initially targeting SMA Type 1 – which is currently in the pivotal stage of development. We have recently initiated a Phase 1 clinical trial to investigate AVXS-101 for the treatment of SMA Type 2. Data from this study will help inform potential future development plans in other SMA subtypes.




The number one genetic cause of infant death is SMA Type 1


years Life expectancy of a child with SMA Type 1

The Goal of AVXS-101

We believe gene therapy is a well-suited approach for the treatment of SMA due to the monogenic nature of the disease—meaning it's caused by the deletion of, or mutations in, a single gene. AVXS-101 is our clinical-stage, proprietary gene therapy candidate of a one-time intravenous treatment for SMA Type 1 and a one-time intrathecal treatment for SMA Type 2 — designed to prevent further muscle degeneration caused by SMA through:

  • Delivery of a fully functional human SMN gene into target motor neuron cells
  • Production of sufficient levels of SMN protein required to improve motor neuron function
  • Rapid onset of effect in addition to sustained SMN protein expression

4 Key Elements of AVXS-101

Discover the components that make AVXS-101 an optimal gene therapy approach.

A non-replicating adeno-associated virus (AAV) capsid is used to deliver a functional copy of a human SMN gene to the patient's own cells without modifying the existing DNA of the patient.

Unlike many other capsids, the AAV9 capsid utilized in AVXS-101 crosses the blood-brain barrier—a tight protective barrier that regulates the passage of substances between the bloodstream and the brain—allowing the option of intravenous administration. AAV9 has been observed in preclinical studies to efficiently target motor neuron cells when delivered via either intrathecal or intravenous administration.

The DNA contained within the capsid shell is engineered to contain the other three critical elements of AVXS-101.

SMA Type 1 Pivotal Trial

The open-label, single-arm, single-dose, multi-center trial – known as STR1VE – is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 in patients with SMA Type 1. The co-primary efficacy outcome measures of the trial include the achievement of independent sitting for at least 30 seconds at 18 months of age; and, event-free survival at 14 months of age. Co-secondary outcome measures include the ability to thrive, and the ability to remain independent of ventilatory support at 18 months of age.

SMA Type 2 Phase 1 Trial

The open-label, dose-comparison, multi-center Phase 1 trial – known as 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, utilizing a one-time IT route of administration. The primary outcome measure for patients less than 24 months of age at the time of dosing is the achievement of the ability to stand without support for at least three seconds. The primary outcome measure for patients between 24 months and 60 months of age at the time of dosing is the achievement of change in Hammersmith Functional Motor Scale Expanded from baseline. The secondary outcome measure for both age groups is the proportion of patients that achieve the ability to walk without assistance, defined as taking at least five steps independently while displaying coordination and balance. Developmental abilities, including motor function, will also be evaluated as exploratory objectives.


Preclinical Development

We have exclusive worldwide license agreements to develop and commercialize gene therapy using the AAV9 vector to treat two rare neurological monogenic disorders: Rett syndrome (RTT) and a genetic form of amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene. We intend to initiate IND-enabling studies in the second half of 2017.

Learn more about clinical trials