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– No new treatment-related safety or tolerability findings –
– No new events reported and 15 of 15 patients event-free at 13.6 months of age; majority of patients receiving proposed therapeutic dose sit unassisted –
– Conference call and webcast
“The completion of our Phase 1 clinical study of AVXS-101, the first ever gene therapy studied for the treatment of SMA Type 1, is an exciting and eagerly awaited milestone, and we are quite pleased with these data,” said
Topline Results from the Phase 1 Trial of AVXS-101 in SMA Type 1
The Phase 1, open-label, dose-escalating study was 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).
No New Treatment-related Safety or Tolerability Concerns Identified: As of
- 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 256 AEs (five treatment-related AEs and 251 non-treatment related AEs) were reported as of
January 20, 2017, following monitoring and source verification. Of these, 52 were determined to be SAEs and 204 were non-serious AEs. As previously noted, two of the 52 SAEs were deemed treatment-related.
- There were 65 new AEs reported after
September 15, 2016, of which 10 were SAEs in three patients and were associated with SMA and were not deemed treatment-related.
No New Events and 15 of 15 Patients Event-Free at 13.6 Months, including 12 of 12 Patients in Proposed Therapeutic-Dose Cohort: As of
- As of
January 20, 2017, 9 of 9 patients -- 3 in the low-dose cohort (Cohort 1) and 6 in Cohort 2 -- reached 20 months of age event free, where the expected event-free rate based on natural history of the disease is 8%.
- As of
January 20, 2017, three patients in Cohort 1 reached 13.6 months of age event-free. As has been previously reported, one patient in Cohort 1 had a pulmonary event in the third quarter of 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 upon independent review to represent progression of disease and not to be related to the use of AVXS-101. This patient completed the final trial visit in September 2016, and as of that time BiPAP use was below the event threshold.
Rapid and Sustained CHOP INTEND Improvements Above Baseline: As of
- 11 out of 12 patients (92%) in Cohort 2 achieved CHOP INTEND scores of at least 40 points.
- 10 out of 12 patients (83%) in Cohort 2 achieved CHOP INTEND scores of at least 50 points.
- 2 out of 12 patients (17%) in Cohort 2 achieved CHOP INTEND scores of at least 60, which is in a range considered to be normal. These two patients achieved the maximum CHOP INTEND score of 64.
Cohort 2 Patients Consistently Achieved and Maintained Key Developmental Motor Milestones: As of
Detailed proposed therapeutic-dose cohort motor milestone data is included in the chart below:
|Motor Milestone Achievement as of January 20, 2017|
|a. Bayley Scales of Infant and Toddler Development, item #20, rolls a minimum 180o from back in only one direction.|
|b. Bayley Scales of Infant and Toddler Development, item #20, rolls a minimum 180o from back to both left and right.|
|c. Sitting unassisted for ≥5 seconds is in accordance with the criteria of item 22 in the Bayley Scales of Infant and Toddler Development – gross motor subtest and surpasses the three second count used as a basis for sitting (test item 1) in the Hammersmith Functional Motor Scale – Expanded for SMA (HFMSE).|
|d. Sitting unassisted for ≥10 seconds is in accordance with the criteria in the World Health Organization – MultiCentre Growth Reference Study.|
|e. Sitting unassisted for ≥30 seconds defines functional independent sitting and is in accordance with the criteria of item 26 in the Bayley Scales of Infant and Toddler Development – gross motor subtest.|
For the end-of-study assessment, all motor milestone achievements above were assessed and adjudicated by an independent third-party reviewer using video evidence.
“These topline data in aggregate for this Phase 1 study suggest a one-time infusion of AVXS-101 appears to be well-tolerated, with a favorable safety profile, and indicate the potential for a clinically transformative effect on event-free survival, rapid and sustained increases in motor function and achievement of motor milestones never observed in the natural history of this disease,” said
Recent Company Highlights
AVXS-101 Accepted into PRIME Program: On
EU Pivotal Trial to Reflect Single-Arm Design: On
Rick Modi Appointed to Senior Management Team as CBO: On
Planned Upcoming Clinical Development Milestones
- Conduct a Type B meeting with the
U.S. Food and Drug Administration( FDA) to discuss chemistry manufacturing and controls (CMC); provide an update based on receipt of meeting minutes in the second quarter of 2017.
- Initiate pivotal trial in U.S. of AVXS-101 via intravenous (IV) delivery in patients with SMA Type 1 in the second quarter of 2017, pending a successful outcome of the Type B CMC meeting.
- Initiate a Phase 1 safety and dose escalation study of AVXS-101 via intrathecal (IT) delivery in patients with SMA Type 2 in the second quarter of 2017, pending a successful outcome of the Type B CMC meeting described above.
- Conduct an end-of-Phase 1 meeting with
FDAin the second or third quarter of 2017.
- Conduct a comprehensive clinical program review with the EMA, to be scheduled in the second or third quarter of 2017.
- Initiate pivotal trial in the EU of AVXS-101 using IV delivery in patients with SMA Type 1 in the second half of 2017.
- Five preclinical and clinical abstracts will be presented at the Annual Meeting of the
American Academy of Neurologyin Boston, April 22-28, 2017, including results from the Phase 1 trial of AVXS-101 in SMA Type 1, including developmental milestones videos.
Fourth Quarter and Full Year 2016 Financial Results
- Cash Position: As of
December 31, 2016, AveXishad $240.4 millionin cash and cash equivalents.
- R&D Expenses: Research and development expenses were
$18.3 millionfor the fourth quarter of 2016 (which included $1.6 millionof non-cash stock-based compensation expense), compared to $8.7 millionfor the same period in 2015 (which included $5.7 millionof non-cash stock-based compensation expense), an increase of $9.6 million. The increase in research and development expenses was primarily attributable to an increase in expenses necessary to support the advancement of the company’s manufacturing product development efforts, clinical and pre-clinical programs, primarily the ongoing trial of AVXS-101 in SMA Type 1, and increases in personnel-related expenses driven by increased headcount across all research, development and manufacturing functions. Partially offsetting the increase in research and development spending was lower non-cash stock-based compensation expense of $4.1 million.
- G&A Expenses: General and administrative expenses were
$7.2 millionfor the fourth quarter of 2016 (which included $2.4 millionof non-cash stock-based compensation expense), compared to $4.4 millionfor the same period in 2015 (which included $1.6 millionof stock-based compensation expense), an increase of $2.8 million. The increase in general and administrative expenses was primarily attributable to an increase in personnel-related expenses driven by increased headcount across all general and administrative functions, legal and professional fees and other infrastructure costs to support the company’s overall growth, and higher non-cash stock-based compensation expense.
- Net Loss: Net loss was
$25.4 million, or $0.92per share, for the fourth quarter of 2016, compared to a net loss of $13.2 million, or $1.82per share, for the fourth quarter of 2015.
Selected Financial Information
|Three Months Ended December 31,||Year Ended December 31,|
|General and administrative||7,198,039||4,428,279||24,522,902||11,079,512|
|Research and development||18,349,344||8,737,246||58,891,667||27,493,460|
|Total Operating Expenses||25,547,383||13,165,525||83,414,569||38,572,972|
|Loss from operations||(25,547,383||)||(13,165,525||)||(83,414,569||)||(38,572,972||)|
|Total Other (Income) Expense||(172,452||)||(4,718||)||(402,765||)||(99,128||)|
|Weighted-average basic and diluted common shares outstanding||27,678,348||7,226,122||22,647,583||7,087,618|
|Basic and diluted net loss per common share||$||(0.92||)||$||(1.82||)||$||(3.67||)||$||(5.43||)|
Balance Sheet Information:
|December 31,||December 31,|
|Cash and cash equivalents||$||240,429,839||$||62,251,860|
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 84652584. The webcast can be accessed live on the Events and Presentations page in the Investors and Media section of the
About the Phase 1 Trial Design
The Phase 1 open-label, dose‑escalation clinical trial of AVXS‑101 in patients with SMA Type 1 initiated in
Patients in the low-dose cohort (n=3) received 6.7E13 vg/kg. Patients in the proposed therapeutic dose cohort (n=12) received 2.0E14 vg/kg. Key inclusion criteria included SMA Type 1 patients with clinical symptoms before six months of age, bi-allelic SMN1 gene deletions or point mutations and with two copies of the SMN2 backup gene, as determined by genetic testing. Of note, all patients in the trial had bi-allelic Exon 7 deletions in SMN1. A key exclusion criteria was the presence of c.859G>C point mutation in SMN2 (Exon 7 modifier). Additionally, patients must have been no older than nine months of age (for the first nine patients) and six months of age (for the last six patients) at the time of vector infusion.
The primary outcome measure was safety and tolerability. The key measures of efficacy were 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).
The primary analysis for efficacy was assessed when all patients reached 13.6 months of age. A follow-up safety analysis will be completed when the last patient reaches 24 months post-dose.
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. SMA 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.
AVXS-101 is a proprietary gene therapy candidate of a one-time treatment for SMA Type 1 and is designed to address the monogenic root cause of SMA and prevent further muscle degeneration by addressing the defective and/or loss of the primary SMN1 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, expectations regarding timing and planned design of the U.S. and EU pivotal trials of AVXS-101 in patients with SMA Type 1, the overall clinical development of AVXS-101, our expectations regarding timing for meetings with regulatory agencies and the potential benefits of AVXS-101 being accepted into the PRIME program. 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" section of AveXis’ Annual Report on Form 10-K for the year ended
All forward-looking statements contained in this press release are expressly qualified by the cautionary statements contained or referred to herein.
Lauren Barbiero W2O Group646-564-2156 email@example.com Investor Inquiries: Jim Goff AveXis, Inc.650-862-4134 firstname.lastname@example.org