· Pivotal Trial of AVXS-101 in SMA Type 1 (STR1VE): The ongoing, open-label, single-arm, single-dose, multi-center trial is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 in patients with SMA Type 1. The trial is expected to enroll a minimum of 15 patients with SMA Type 1 who are less than six months of age at the time of gene therapy, and who have one or two copies of the SMN2 backup gene as determined by genetic testing and bi-allelic SMN1 gene deletion or point mutations. Three patients have been dosed to date.
· Phase 1 Trial of AVXS-101 in SMA Type 2 (STRONG): The on-going, open-label, dose-comparison, multi-center Phase 1 trial 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 intrathecal (IT) route of administration. The trial is expected to enroll 27 infants and children who are symptomatic 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. One patient has been dosed to date.
Planned Trials in SMA
· Pivotal Trial of AVXS-101 in SMA Type 1 in Europe (STR1VE EU): The planned trial is expected to reflect a single-arm design, using natural history of the disease as a comparator, and is expected to enroll approximately 30 patients with SMA Type 1 who are less than six months of age at the time of gene therapy. The trial is designed to evaluate safety and efficacy of a one-time IV dose of AVXS-101, including achievement of motor milestones, specifically patients ability to sit unassisted, as well as an efficacy measure defined by the time from birth to an event, 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. AveXis incorporated scientific advice from the European Medicines Agency into the protocol design, and expects to initiate the trial in the first half of 2018.
· Pre-Symptomatic SMA Types 1, 2, 3 (SPRINT): The planned multi-national trial is expected to enroll approximately 44 patients with two, three and four copies of SMN2 who are less than six weeks of age and pre-symptomatic at the time of gene therapy. The trial is designed to evaluate appropriate clinical endpoints, including developmental milestones, survival, bulbar function and safety, of a one-time IV infusion of AVXS-101. AveXis expects to initiate the trial in the first half of 2018, and will provide more design details at the time of initiation.
· Pediatric All Comers with SMA Types 1, 2, 3 (REACH): The planned multi-national trial is expected to enroll approximately 50 patients between approximately six months and 18 years of age who do not qualify for other AVXS-101 trials at the time of gene therapy. The trial is designed to evaluate a one-time IT dose of AVXS-101. AveXis expects to initiate the trial in late Q4 2018 or early 2019, and will provide more trial design details at the time of initiation.
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.