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AVEXIS, INC. filed this Form 10-K on 02/28/2018
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The self‑complementary modification overcomes this rate‑limiting step of cell‑mediated second‑strand synthesis, as the two complementary halves of the scAAV genomes will associate with each other to form the required double‑stranded DNA unit.


A continuous promoter:  this agent activates the transgene and is designed to allow for continuous and sustained SMN gene expression. The cytomegalovirus enhanced chicken beta‑actin hybrid promoter that we utilize is a constitutive, or “always on” promoter that has been observed to increase transgene expression from AAV vectors compared to other promoters.

Clinical Development of AVXS‑101

We are currently developing AVXS‑101 for the treatment of SMA Type 1 through intravenous administration and SMA Type 2 for intrathecal administration. We intend to initiate three additional studies to further evaluate AVXS-101, including in new SMA patient populations.

Pivotal Clinical Trial for SMA Type 1

In September 2017, based on the FDA's review of our clinical, non-clinical and chemistry, manufacturing and controls, or CMC, data, including a potency assay of AVXS-101, we initiated our pivotal trial of AVXS-101 for patients with SMA Type 1 using the IV formulation produced using our current good manufacturing practice, or cGMP, commercial manufacturing process. Five patients have been dosed in this clinical trial to date.

          The open-label, single-arm, single-dose, multi-center trial, which we call STR1VE, is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 of 1.1 × 1014 vg/kg, which is intended to be equivalent to the proposed therapeutic dose received by the second dosing cohort in our Phase 1 clinical trial of AVXS-101 in patients with SMA Type 1.

          The trial will enroll a minimum of 15 patients with SMA Type 1 who are less than six months of age at the time of gene therapy, and who have one or two copies of the SMN2 backup gene as determined by genetic testing and bi-allelic SMN1 gene deletion or point mutations. Following dosing of the first three patients in the trial, we conducted a review of the safety data of AVXS-101 from six time points (days one, two, seven, 14, 21 and 30), as well as early signals of efficacy.  Based on our review and discussion with the FDA, we have initiated screening for, and begun enrolling, the remaining patients in the trial in accordance with the trial protocol.

          The intent-to-treat, or ITT, population is defined as patients who are less than six months of age and symptomatic at the time of gene therapy, with two copies of the SMN2 gene as determined by genetic testing, bi-allelic SMN1 gene deletion and no c.859G>C mutation in SMN2. The intended enrollment will include at least 15 patients that meet the ITT criteria. The first three patients will be ITT patients per the trial protocol definition and will be dosed four weeks apart to assess safety and efficacy using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders, or CHOP INTEND.

          The co-primary efficacy outcome measures of the trial will include:


The achievement of the developmental milestone of independent sitting for at least 30 seconds at 18 months of age; and 


Event-free survival at 14 months of age, with an event defined as either 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.



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