| Title: |
P.065 AVXS-101 gene-replacement therapy (GRT)) in presymptomatic spinal muscular atrophy (SMA): study update |
| Authors: |
Schultz, M; Swoboda, K; Farrar, M; McMillan, H; Parsons, J; Farrow, M; Ogrinc, FG; Feltner, DE; McGill, BE; Spector, SA; L’Italien, J; Sproule, DM; Strauss, KA |
| Source: |
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ; volume 46, issue s1, page S31-S32 ; ISSN 0317-1671 2057-0155 |
| Publisher Information: |
Cambridge University Press (CUP) |
| Publication Year: |
2019 |
| Description: |
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of 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 (2x SMN2 ) 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 enrolling ≥27 SMA patients with 2–3x SMN2 . Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1x1014 vg/kg). Safety and efficacy are assessed through study end (18 [2x SMN2 ] or 24 months [3x SMN2 ]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2x SMN2 ]) or assisted standing (24 months [3x SMN2 ]). Results: From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2x SMN2 ) at ages 8–37 days. Mean baseline 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). 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1017/cjn.2019.165 |
| Availability: |
https://doi.org/10.1017/cjn.2019.165; https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0317167119001653 |
| Rights: |
https://www.cambridge.org/core/terms |
| Accession Number: |
edsbas.109C87D9 |
| Database: |
BASE |