RT Journal Article
SR Electronic
T1 014 AVXS-101 gene-replacement therapy (GRT) in presymptomatic spinal muscular atrophy (SMA): study update
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP A5
OP A6
DO 10.1136/jnnp-2019-anzan.14
VO 90
IS e7
A1 Michelle Farrar
A1 Kathryn J Swoboda
A1 Meredith Schultz
A1 Hugh McMillan
A1 Julie Parsons
A1 Ian E Alexander
A1 Elaine Kernbauer
A1 Marcia Farrow
A1 Francis G Ogrinc
A1 Douglas E Feltner
A1 Bryan E McGill
A1 Sidney A Spector
A1 James L’Italien
A1 Douglas M Sproule
A1 Kevin A Strauss
YR 2019
UL http://jnnp.bmj.com/content/90/e7/A5.3.abstract
AB Introduction SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron 1 gene (SMN1). Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns.Methods SPR1NT is a multicenter, open-label, phase 3 study (NCT03505099) enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1×1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]).Results From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). As of January 31, 2019, 15 asymptomatic infants have been enrolled in SPR1NT and dosed with AVXS-101. Updated data available at the time of the congress will be presented.Conclusions Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.