AveXis Announces New England Journal of Medicine Publication of Phase 1 Data of AVXS-101 Gene Replacement Therapy in Spinal Muscular Atrophy Type 1

– Patients who received a single dose of AVXS-101 resulted in longer
survival, superior achievement of motor milestones, and better motor
function than in historical cohorts –

– As of August 7, 2017, all patients are alive, event-free and have
reached at least 20 months of age –

– As of August 7, 2017, all patients who received the proposed
therapeutic dose of AVXS-101 demonstrated continued treatment durability
and achievement of motor milestones, including 75 percent of these
patients now sitting for 30 seconds or longer –

CHICAGO–(BUSINESS WIRE)–AveXis, Inc. (NASDAQ:AVXS), a clinical-stage gene therapy company
developing treatments for patients suffering from rare and
life-threatening neurological genetic diseases, announced data as of
August 7, 2017, from the Phase 1 trial of AVXS-101 in patients with
spinal muscular atrophy (SMA) Type 1 were published today in the New
England Journal of Medicine
(NEJM) in a paper titled “Single-Dose
Gene-Replacement Therapy for Spinal Muscular Atrophy.” These data
demonstrate that all patients who received a one-time intravenous dose
of AVXS-101 are alive and event-free at 20 months of age. Natural
history indicates that only eight percent of untreated patients with SMA
Type 1 will survive event-free at 20 months of age. The publication may
be found online at www.nejm.org/doi/full/10.1056/NEJMoa1706198.

It is incredibly encouraging to see that all children who have received
AVXS-101 remain event-free and demonstrate a durable treatment effect at
20 months of age and older, including in many cases achievement of new
developmental milestones,” Sean Nolan, President and Chief Executive
Officer of AveXis. “To have these Phase 1 data published in the
prestigious New England Journal of Medicine highlights the
groundbreaking work of Dr. Jerry Mendell and his team and further
validates the clinically transformative nature of gene therapy in
children with SMA Type 1.”

The NEJM publication provides detailed data as of August 7, 2017, from
the Phase 1, open-label, dose-escalating study, designed to evaluate the
safety and tolerability of AVXS-101 in patients with SMA Type 1. The key
measures of efficacy were the time from birth to an “event,” which was
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, and video confirmed
achievement of ability to sit unassisted. Additionally, several
exploratory objective measures were assessed, including a standard motor
milestone development survey and Children’s Hospital of Philadelphia
Infant Test of Neuromuscular Disorders (CHOP INTEND).

Event-free Survival and Safety

  • Data as of August 7, 2017, showed no new events, and 15 of 15 (100%)
    patients were event-free at 20 months of age. The expected event-free
    survival rate at 20 months of age based on the natural history of the
    disease is eight percent. The median age at last follow-up was 25.7
    months and 30.7 months for patients in the proposed therapeutic-dose
    cohort (Cohort 2) and low-dose cohort (Cohort 1), respectively.

    • As has been previously reported, a total of five adverse events
      (AEs) in four patients were deemed treatment-related. Of these,
      two were serious adverse events (SAEs) experienced by two
      patients, and three were non-serious AEs experienced by two
      patients. All consisted of clinically asymptomatic liver enzyme
      elevations and were resolved with prednisolone treatment. There
      were no clinically significant elevations of gamma-glutamyl
      transferase, alkaline phosphatase or bilirubin and, as such, Hy’s
      Law was not met. Other non-treatment-related AEs were expected and
      were associated with SMA.
    • A cumulative total of 297 AEs (five treatment-related AEs and 292
      non-treatment related AEs) were reported as of August 7, 2017,
      following monitoring and source verification. Of these, 56 were
      determined to be SAEs and 241 were non-serious AEs.
  • AVXS-101 appeared to have a favorable safety profile and to be
    generally well tolerated, with no new treatment-related safety or
    tolerability concerns identified.

Treatment Durability and Motor Milestone

  • As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 have
    achieved and maintained CHOP-INTEND scores of ≥40 points.
  • As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 achieved
    head control, nine of 12 patients (75%) could roll over and 11 of 12
    patients (92%) could sit with assistance.
  • As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 could sit
    unassisted for at least five seconds, 10 of 12 patients (83%) could
    sit unassisted for at least 10 seconds and nine of 12 patients (75%)
    could sit unassisted for 30 seconds or more.
  • As of August 7, 2017, two patients in Cohort 2 could crawl, pull to a
    stand and stand and walk independently.

    • All motor milestones have been assessed and adjudicated by an
      independent third-party reviewer using video evidence.




Age at








  Event-free Survival and Motor and Other Milestones Among the 12
Patients in Cohort 2
as of August 7, 2017*












Sits with


  Sits Unassistedc   Other Achievements









  Speaks   Swallows  








E.04   5.6   31.1   +   +   +   +   +           +   +        
E.05   4.2   28.5   +   +   +   +   +   +   +   +   +   +   +
E.06   1.9   26.1   +   +   +   +   +   +   +   +   +   +   +
E.07   3.6   28.1   +   +   +   +   +   +       +   +   +    
E.08   7.9   32.4   +                                        
E.09   4.9   28.9   +   +   +   +   +   +   +   +   +   +   +
E.10   0.9   25.3   +   +   +   +   +   +   +   +   +   +   +
E.11   2.3   23.8   +   +   +   +   +   +   +   +   +        
E.12   2.6   23.9   +   +   +   +   +   +   +   +   +   +   +
E.13   0.9   22.1   +   +       +   +   +   +   +   +        
E.14   4.1   22.0   +   +   +   +   +   +   +   +   +   +   +
E.15   2.1   20.6   +   +       +   +   +   +   +   +        

Patient with

outcome (%)

This Study   100   100   92   75   92   92   83   75   92   92   58   50
Natural History  

8 by 20


  NA   0   0**   0**   0**   0**   0**   NA   NA   NA  

8 by 20


*At baseline, none of the patients in Cohort 2 had achieved any of
the listed motor milestones except for bringing a hand to the mouth.
As of August 7, 2017, the majority of these patients had reached at
least one major motor milestone. No patients in Cohort 1 are listed,
since none attained any motor milestones. NA denotes not available,
and NIV noninvasive ventilation. Plus signs indicate achievement of
      a.   Event-free survival (the primary efficacy outcome) was defined as
the age at the end of the study at which patients were free of
ventilatory support, which was defined as the need for ventilation
for at least 16 hours per day for at least 14 consecutive days.
b. According to item 20 on the Bayley Scales of Infant and Toddler
Development, rolling over is defined as movement of at least 180
degrees both left and right from a position of lying on the back.
c. Sitting unassisted for at least 5 seconds is in accordance with the
criteria of item 22 on the Bayley Scales of Infant and Toddler
Development gross motor subtest and surpasses the 3-second count
that is used as a basis for sitting (test item 1) on the Hammersmith
Functional Motor Scale–Expanded for Spinal Muscular Atrophy (SMA).
Sitting unassisted for at least 10 seconds is in accordance with the
criteria used in the World Health Organization Multicentre Growth
Reference Study. Sitting unassisted for at least 30 seconds defines
functional independent sitting and is in accordance with the
criteria of item 26 on the Bayley Scales of Infant and Toddler
Development gross motor subtest.
d. Nutritional support refers to the placement of either a gastrostomy
tube or a nasogastric tube, as determined by the preference of the
parents or the primary physician. Once enrolled in the study, all
the patients who required nutritional support underwent
gastrostomy-tube placement, and none were removed during the study.
e. Data are from Finkel et al.
** Data are from De Sanctis et al.

Nutritional and Respiratory Support

  • According to natural history of the disease, nearly all Type 1
    patients require nutritional and respiratory support by 12 months of
    age, and are not able to swallow or speak effectively.
  • As of August 7, 2017, patients who were free of respiratory or feeding
    support on January 20, 2017, continued without the need for supportive

    • As of August 7, 2017, six of seven (86%) patients in Cohort 2 that
      did not require feeding support before treatment continued without
      feeding support after treatment; seven of 10 (70%) patients that
      did not require bi-level positive airway pressure (BiPAP) support
      before treatment did not require BiPAP support at last assessment.
    • As of August 7, 2017, eleven of 12 (92%) patients in Cohort 2 were
      fed orally, and six of 12 (50%) patients were exclusively fed
  • Further, as of August 7, 2017, eleven of 12 (92%) patients were able
    to speak; three more patients than previously reported on April 25,
    2017 at the American Academy of Neurology.

AveXis and my team at Nationwide Children’s Hospital have worked
tirelessly to alter the inevitable course of SMA Type 1,” Jerry Mendell,
MD, principal investigator in the Center for Gene Therapy at Nationwide
Children’s Hospital. “We are proud to see these data published in New
England Journal of Medicine,
representing the culmination of decades
of dedication and commitment to making a better life possible for the
children diagnosed with this unforgiving condition.”

AVXS-101 is currently being evaluated in a pivotal trial for the
treatment of SMA Type 1.

About SMA

SMA is a severe neuromuscular disease characterized by the loss of motor
neurons leading to progressive muscle weakness and paralysis. SMA is
caused by a genetic defect in the SMN1 gene that codes SMN, a protein
necessary for survival of motor neurons. The incidence of SMA is
approximately one in 10,000 live births and is the leading genetic cause
of infant mortality.

The most severe form of SMA is Type 1, a lethal genetic disorder
characterized by motor neuron loss and associated muscle deterioration,
which results in mortality or the need for permanent ventilation support
before the age of two for greater than 90 percent of patients. SMA Type
2 typically presents between six and 18 months of age and affected
patients can sit unassisted but never walk or stand without support.

About AVXS-101

AVXS-101 is a proprietary gene therapy candidate of a one-time treatment
for SMA Types 1 and 2, designed to address the monogenic root cause of
SMA and prevent further muscle degeneration by addressing the defective
and/or loss of the primary SMN gene. AVXS-101 also targets motor
neurons, providing rapid onset of effect and crossing the blood brain
barrier to allow effective targeting of both central and systemic

About AveXis, Inc.

AveXis is a clinical-stage gene therapy company developing treatments
for patients suffering from rare and life-threatening neurological
genetic diseases. The company’s initial proprietary gene therapy
candidate, AVXS-101, is in the pivotal phase of study for the treatment
of SMA Type 1, and a Phase 1/2a study for SMA Type 2. The company also
intends to expand the study of gene therapy into two additional 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.

For additional information, please visit www.avexis.com.

Forward-Looking Statements

This press release contains “forward-looking statements,” within the
meaning of the Private Securities Litigation Reform Act of 1995,
regarding, among other things, AveXis’ research, development and
regulatory plans for AVXS-101, including the potential of AVXS-101 to
alter the course of disease in patients with SMA Type 1, AveXis’ ongoing
clinical trial of AVXS-101 in SMA Type 1 and plans to expand AveXis’
research, development efforts to explore potential treatments of RTT and
genetic ALS. Such forward-looking statements are based on current
expectations and involve inherent risks and uncertainties, including
factors that could delay, divert or change any of them, and could cause
actual results to differ materially from those projected in its
forward-looking statements. Meaningful factors which could cause actual
results to differ include, but are not limited to, the scope, progress,
expansion, and costs of developing and commercializing AveXis’ product
candidates; regulatory developments in the U.S. and EU, as well as other
factors discussed in the “Risk Factors” and the “Management’s Discussion
and Analysis of Financial Condition and Results of Operations” sections
of AveXis’ Annual Report on Form 10-K for the year ended December 31,
2016, filed with the SEC on March 16, 2017, and AveXis’ Quarterly Report
on Form 10-Q for the quarter ended June 30, 2017, filed with the SEC on
August 10, 2017. In addition to the risks described above and in the
Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current
Reports on Form 8-K and other filings with the SEC, other unknown or
unpredictable factors also could affect AveXis’ results. There can be no
assurance that the actual results or developments anticipated by AveXis
will be realized or, even if substantially realized, that they will have
the expected consequences to, or effects on, AveXis. Therefore, no
assurance can be given that the outcomes stated in such forward-looking
statements and estimates will be achieved.

All forward-looking statements contained in this press release are
expressly qualified by the cautionary statements contained or referred
to herein. AveXis cautions investors not to rely too heavily on the
forward-looking statements AveXis makes or that are made on its behalf.
These forward-looking statements speak only as of the date of this press
release (unless another date is indicated). AveXis undertakes no
obligation, and specifically declines any obligation, to publicly update
or revise any such forward-looking statements, whether as a result of
new information, future events or otherwise, except as required by law.


Media Inquiries:
W2O Group
Lauren Barbiero, 646-564-2156
AveXis, Inc.
Jim Goff, 650-862-4134