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– The trial will evaluate safety, dosing and proof of concept for efficacy –
– The trial will use product produced from the new GMP process at the
– Conference call and webcast today at
“We are quite pleased to initiate our first trial of AVXS-101 in patients with SMA Type 2,” said
U.S. Phase 1 Trial in SMA Type 2 (STRONG)
The open-label, dose-comparison, multi-center Phase 1 trial – known as STRONG – is designed to evaluate the safety, optimal dosing, and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The trial will enroll 27 infants and children with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2 genetic modifier, who are able to sit but have no historical or current ability to stand or walk.
Two dosage strengths will be evaluated and patients will be stratified into two age groups: patients less than 24 months, and patients at least 24 months but less than 60 months. There will be at least a four-week interval between the dosing of the first three patients for each dose being studied and, based on the available safety data, a decision will be made whether to proceed.
- Cohort 1 (Dose A) will receive a dose of 6.0 x 1013 vg of AVXS-101 and enroll three patients less than 24 months of age.
- If safety is established according to the Data Safety Monitoring Board (DSMB), the study will proceed to Cohort 2.
- Cohort 2 (Dose B) will receive a dose of 1.2 X 1014 vg of AVXS-101 and enroll three patients less than 60 months of age.
- If safety is established according to the DSMB, an additional 21 patients will be enrolled until there are a total of 12 patients less than 24 months, and 12 patients at least 24 months but less than 60 months of age, who have received Dose B.
According to the well-characterized natural history of the disease by the Pediatric Neuromuscular Clinical Research Network, 100 percent of children with SMA Type 2 will never walk without support, 95 percent of children will never stand without assistance and more than 30 percent will die by 25 years of age. Additionally, children with SMA Type 2 experienced a mean decrease of - 0.33 points on the Hammersmith Function Motor Scale Expanded over a 12-month period.
Outcome Measures for Patients Less than 24 Months of Age
- The primary outcome measure for patients less than 24 months of age at the time of dosing is the achievement of the ability to stand without support for at least three seconds.
- The secondary outcome measure is the proportion of patients who achieve the ability to walk without assistance, defined as taking at least five steps independently while displaying coordination and balance.
- Developmental abilities, including motor function, will be evaluated as exploratory objectives.
Outcome Measures for Patients Between 24 and 60 Months of Age
- The primary outcome measure for patients between 24 months and 60 months of age at the time of dosing is the achievement of change in Hammersmith Functional Motor Scale Expanded from baseline.
- The secondary outcome measure is the proportion of patients who achieve the ability to walk without assistance, defined as taking at least five steps independently displaying coordination and balance.
- Developmental abilities, including motor function, will be evaluated as exploratory objectives
The trial is projected to be conducted at 11 sites in
For more information about these clinical trials, please visit clinicaltrials.gov.
“This Phase 1 trial in children with SMA Type 2 will allow us to evaluate safety, optimal dosing and proof-of-concept for efficacy of AVXS-101 compared to the well-characterized natural history using the one-time intrathecal route of administration,” said Dr.
SMA Type 1 Update
Today’s Conference Call Information
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 those affected will never walk without support and most will never stand without support. SMA Type 2 results in mortality in more than 30 percent of patients by the age of 25.
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 targeting of both central and systemic features.
For additional information, please visit www.avexis.com.
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 patients with SMA Type 1 and SMA Type 2, the expected timing of the initiation of AveXis’ planned clinical trial in SMA Type 2, ability to enroll for, and the results of, AveXis’ planned clinical trials in SMA Type 1 and SMA Type 2, the overall clinical development of AVXS-101, if approved, AveXis’ research, development and regulatory plans for AVXS-101, including AveXis’ commercial manufacturing process, timing of feedback from
All forward-looking statements contained in this press release are expressly qualified by the cautionary statements contained or referred to herein.