Rare Daily Staff
        
The U.S. Food and Drug Administration notified AveXis that it may initiate its planned pivotal trial of AVXS-101, its gene therapy for patients with spinal muscular atrophy type 1, a severe, progressive neuromuscular disease that is fatal.

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 condition is characterized by motor neuron loss and associated muscle deterioration, which results in mortality or the need for permanent ventilation support before age 2 for greater than 90 percent of patients.

Chicago-based AveXis said it plans to initiate the trial of its gene therapy immediately. 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. The company said 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.

The open-label, single-arm, single-dose, multi-center trial in SMA type 1 is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101. The trial will 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.

The co-primary efficacy outcome measures of the trial will include the achievement of the developmental milestone of independent sitting for at least 30 seconds at 18 months of age, and event-free survival at 14 months of age (with an event 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).

Co-secondary outcome measures will include the ability to remain independent from feeding support, tolerate thin liquids, and maintain weight. It will also include the ability to remain independent of ventilatory support at 18 months of age. 

The company is continuing discussions with the FDA for the planned clinical trial in patients with SMA type 2. The company expects to provide an update on that program will be provided in the fourth quarter of 2017.

October 2, 2017

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