THE ONLY SMA GENE THERAPY IN HUMAN TRIALS

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 Type 1

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 and then progressively moving to other SMA subtypes. Here's why we're targeting Type 1 first:

60

60% of SMA patients have Type 1 WITH OBSERVATION OF DISEASE SYMPTOMS WITHIN SIX MONTHS OF BIRTH

1

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

<2

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—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.

Phase 1 Trial

The open-label study is designed to evaluate safety and efficacy of AVXS-101 in patients suffering from SMA Type 1. The primary outcome in the study is safety and tolerability. The secondary outcome measure is an efficacy measure as defined by the time from birth to an “event,” which is defined as death or at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively. Exploratory outcome measures include muscle assessment studies, measured by a patient’s CHOP-INTEND score.