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In the interim analysis presented at the meeting, gene therapy appeared to reduce the need for ventilation support and allowed patients to successfully recover from respiratory illnesses that are often lethal to SMA Type 1 patients. The interim analysis found that none of the patients in either dosing cohort required permanent ventilation as of
Dr. Shell said, “The progression of SMA Type 1 is such that respiratory failure is the predominant cause of death. To see no patients requiring permanent ventilatory support is encouraging. We are pleased to see the two children hospitalized during a challenging respiratory season in the first three months of 2016 recover from their illness, as children with SMA type 1 rarely recover so quickly from such illnesses and often require permanent ventilation support as a sequelae.”
In addition, AVXS-101 continued to demonstrate a favorable safety profile in patients studied as of
The natural history of SMA Type 1 indicates that bulbar muscle weakness, skeletal muscle weakness in the neck and intercostal muscle weakness lead to respiratory impairment, poor clearance of airway secretions, risk of aspiration and recurrent infections leading to death or permanent ventilation. The median age to permanent ventilation or death in a published natural history study of SMA type 1 patients is 10.5 months (IQR 8.1-13.6 months), and by 13.6 months only 25 percent of SMA Type 1 patients are alive and free of permanent ventilation1.
In the ongoing trial, as of
- No patient required permanent ventilation with the median age of all 15 patients at 14.9 months.
- 8 of 10 (80%) patients that did not use biphasic/bi-level ventilation (BiPAP) support before gene transfer continued without any ventilation support (the two exceptions being after severe illness/hospitalizations in the first quarter of 2016 to assist recovery).
“The preliminary data appear to indicate AVXS-101 may have a positive impact on the pulmonary outcomes of patients in the trial suffering from SMA Type 1, which may be impacting the overall survival benefit,” said
Phase 1 Trial Design
The Phase 1 open-label, dose-escalation study is designed to evaluate safety and preliminary indications of efficacy of AVXS-101 in patients suffering from SMA Type 1. The primary outcome in the study is safety and tolerability. The secondary outcome measure is efficacy as defined by the time from birth to an “event,” with an event defined as death or until a patient requires at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of an acute reversible illness or perioperatively. Exploratory outcome measures include motor function testing, measured by the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a test developed to measure motor skills of patients with SMA Type 1, and other motor milestone development surveys and tests.
The clinical protocol requires that each patient receive a one-time dosage of AVXS-101, by intravenous injection over a one-hour period. The patient remains at the clinical trial site for 48 hours after dosing for monitoring prior to discharge, and weekly follow-up evaluations are conducted for one month after dosing. After the first month, additional evaluations are conducted monthly for 23 months.
The trial has fully-enrolled with a total of 15 patients who met enrollment criteria of diagnosis of SMA Type 1 before six months of age, with two copies of the SMN2 backup gene, as determined by genetic testing. The trial includes two dosing cohorts:
- Cohort 1 (low dose) includes three patients dosed at (6.7 X1013 vg/kg), aged 5.9 to 7.2 months at time of dosing;
- Cohort 2 (proposed therapeutic dose) includes 12 patients dosed at (2.0 X1014 vg/kg), aged 0.9 to 7.9 months at time of dosing.
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, intravenous 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 intravenous (IV) dosing route and effective targeting of both central and systemic features.
1. Finkel, R. et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology 83,810–817 (2014).
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 expected timing for reporting results from the ongoing Phase 1 clinical trial and the potential for AVXS-101 to positively impact the pulmonary and nutritional support of patients suffering from 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 to herein.
Lauren Barbiero W2O Group646-564-2156 email@example.com Investor Inquiries: Jim Goff AveXis, Inc.650-862-4134 firstname.lastname@example.org