AveXis Announces Plan to Initiate Pivotal Trial of AVXS-101 in SMA Type 1 Using Product from New GMP Commercial Process

Chicago, Ill. (September 29, 2017) – AveXis, Inc. (NASDAQ: AVXS), a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today announced the U.S. Food and Drug Administration (FDA) has notified the company that based on review of data submitted, including the potency assay, it may initiate its planned pivotal trial of AVXS-101 for patients with spinal muscular atrophy (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.

“We are pleased to reach this outcome following a thorough review by the FDA of the voluminous information we supplied to address the commitments made during the Chemistry, Manufacturing, and Controls Type B meeting in May, and are eager to initiate our pivotal trial of AVXS-101 in SMA Type 1 in the U.S. using product from our GMP process,” said Sean Nolan, President and Chief Executive Officer of AveXis. “Moving AVXS-101 back into the clinic, as planned, with product from our GMP process is a significant milestone, not only for AveXis but also for the patients we hope to serve.”

The AveXis facility is the production site to supply the pivotal and future trials and, should AVXS-101 be approved for marketing, to meet projected commercial demand. With the pivotal trial now starting, AveXis and the FDA are continuing discussions on key topics, including dosing, for intrathecal administration of AVXS-101 for the planned clinical trial in patients with  SMA Type 2. An update on this program will be provided in the fourth quarter of 2017.

U.S. Pivotal Trial in SMA Type 1 (STR1VE)
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 of 1.1 x 1014 vg/kg, which is equivalent to the proposed therapeutic dose received by the second dosing cohort in the Phase 1 trial, in patients with SMA Type 1. Based on the data derived from the company’s new analytical methods that were submitted and reviewed by FDA, it has been determined through direct test with the improved PCR method that the dose used in AveXis’ Phase 1 trial of AVXS-101 in SMA Type 1 was 1.1 x 1014 vg/kg. Additionally, extensive testing in the SMN delta 7 mouse potency assay has demonstrated the equivalence of dose response between the products produced by the Phase 1 and Phase 3 manufacturing process. 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. There will be at least a four-week dosing interval between dosing of the first three patients to allow review of the safety analysis from six time points (days one, two, seven, 14, 21 and 30), as well as early signals of efficacy, prior to dosing of the next patient. The intent-to-treat 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 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.

Co-secondary outcome measures will include:

• The ability to thrive, defined as the ability to: remain independent from feeding support,
  tolerate thin liquids and maintain weight; and,
• The ability to remain independent of ventilatory support at 18 months of age.

The trial is projected to be conducted at 16 sites in the United States, including: Ann and Robert H. Lurie Children’s Hospital of Chicago, Boston Children’s Hospital, Children’s Hospital Colorado, Children’s Hospital of Philadelphia, Columbia University, David Geffen School of Medicine at UCLA, Duke University, Johns Hopkins Pediatric Neurology, Nationwide Children’s Hospital, Oregon Health and Science University, Stanford University Medical Center, University of Central Florida College of Medicine, University of Texas Southwestern Medical Center, University of Utah, University of Wisconsin, and Washington University School of Medicine.

“We are appreciative of the detailed reviews and timely feedback we have received from the FDA,” said James L’Italien, PhD, Chief Regulatory and Quality Officer for AveXis. “We look forward to our end-of- Phase 1 meeting, which has been scheduled for late in the fourth quarter, to discuss next steps in the regulatory process for AVXS-101.”