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-- Majority of patients on the proposed therapeutic dose achieved key developmental milestones including sitting unassisted; two patients walking independently --
-- Conference call and webcast
For the first time, interim data from the trial were presented that
highlighted patient achievement of key motor development milestones as
“To date, the majority of patients who received the proposed therapeutic
dose of AVXS-101 have achieved key milestones and two-thirds of these
patients can sit independently – a fact completely inconsistent with the
known disease course, as children with untreated SMA Type 1 will never
sit unassisted,” said
Interim Phase 1 Data as of
Data as of
September 15, 2016showed AVXS-101 continued to demonstrate a favorable safety profile and was generally well tolerated, with no new treatment-related safety or tolerability concerns identified.
There has been a cumulative total of 118 adverse events (AEs)
reported as of
September 15, 2016, 34 of which were determined to be serious adverse events (SAEs) and 84 were determined to be non-serious AEs. As previously reported, a total of 5 AEs in 4 patients were treatment-related. Two were deemed treatment-related SAEs (experienced by 2 patients) and three were deemed non-serious AEs (experienced by 3 patients). All consisted of clinically asymptomatic liver enzyme elevations.
- All of the elevated liver enzyme AEs and SAEs were clinically asymptomatic and resolved with prednisolone treatment. There were no clinically significant elevations of gamma-glutamyl transferase (GGT), 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.
- There has been a cumulative total of 118 adverse events (AEs) reported as of
All patients in Cohort 2 (proposed therapeutic dose) are event-free,
defined as death or requiring at least 16 hours per day of ventilation
support for breathing for greater than two weeks in the absence of an
acute reversible illness, or perioperatively. The median age at last
follow-up for Cohort 2 is 17.3 months, with the oldest patient at 27.4
months of age.
As previously reported, one patient in Cohort 1 (the low-dose
cohort) did have a pulmonary event after
July 1, 2016. The patient had increased use of bi-level positive airway pressure (BiPAP) in advance of surgery related to hypersalivation, a condition experienced by some SMA patients; the event was determined by independent review to represent progression of disease and not to be related to the use of AVXS-101.
- As previously reported, one patient in Cohort 1 (the low-dose cohort) did have a pulmonary event after
Mean increases in CHOP-INTEND scores of 9.0 points in Cohort 1 and
24.8 points in Cohort 2 were observed, reflecting improvement in motor
function. The Children’s Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP-INTEND) is a test developed to measure
motor skills of patients with SMA Type 1.
- 11 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 40 points.
- 9 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 50 points.
- 3 out of 12 patients in Cohort 2 achieved CHOP-INTEND scores of at least 60, which is in a range considered to be normal.
Patients on the proposed therapeutic dose of AVXS-101 consistently
achieved and maintained key developmental motor milestones.
September 15, 2016, 11 out of 12 patients achieved head control; 7 out of 12 patients could roll over (completely); 11 out of 12 patients could sit with support; and 8 out of 12 patients could sit unassisted, including one patient whose achievement of this milestone was confirmed after September 15.
In addition, 7 patients are able to feed themselves, including one
patient whose achievement of this milestone was confirmed after
September 15, and 5 patients are speaking (1 bilingual).
4 patients are now standing with support, including two whose
achievements of this milestone were confirmed after
2 patients are now walking independently, including one whose
achievement of this milestone was confirmed after
September 15. These two patients each achieved earlier and important developmental milestones such as crawling, standing with support, standing alone and walking with support.
- As of
Detailed Cohort 2 motor milestone data is included in the chart below:
|Motor Milestone Achievement as of September 15, 2016|
|Age at Gene Transfer (mos)||Brings Hand to Mouth||Head Control||Rolls Over (partial)||Rolls Over (complete)||
* Achievement confirmed after
“The preliminary clinical observations of extended event-free survival,
sustained increases in motor function and achievement of developmental
milestones in patients receiving a one-time infusion of AVXS-101 have
far exceeded what has been observed with natural history,” said
Conference Call Information
Analysts and investors can participate in the conference call by dialing
(844) 889-6863 for domestic callers and (661) 378-9762 for international
callers, using the conference ID 93427499. The webcast can be accessed
live on the Events and Presentations page in the Investors and Media
section of the
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.
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 1 is the leading genetic cause of infant mortality.
AVXS-101 is a proprietary gene therapy candidate of a one-time treatment for SMA Type 1 and is the only clinical-stage gene therapy in development for SMA. AVXS-101 is designed to address the monogenetic 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 crosses the blood brain barrier allowing an IV dosing route and effective targeting of both central and systemic features.
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
positively impact quality of life and alter the course of disease in
children with SMA Type 1. 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
All forward-looking statements contained in this press release are
expressly qualified by the cautionary statements contained or referred