One-Time Intrathecal (IT) Administration of AVXS-101 IT Gene Therapy for Spinal Muscular Atrophy: Phase 1 Study (STRONG)


Clinical Trials

Poster Number: 52


Richard Finkel, MD, John Day, MD, PhD, Basil Darras, MD, Nancy Kuntz, MD, PhD, Anne Connolly, MD, Thomas Crawford, MD, Russell Butterfield, MD, PhD, Perry Shieh, MD, PhD, Gihan Tennekoon, MD, Susan T. Iannaccone, MD, Matthew Meriggioli, Sitra Tauscher-Wisniewski, MD, John Shoffner, Francis G. Ogrinc, Sarah Kavanagh, Elaine Kernbauer, JoAnn Whittle, Douglas M. Sproule, Douglas E. Feltner, Jerry R. Mendell


1. Nemours Children’s Hospital, University of Central Florida College of Medicine, 2. Stanford, 3. Boston Children's Hospital, 4. Lurie Children's Hospital - Chicago, 5. Nationwide Children's Hospital, 6. The Johns Hopkins University School of Medicine, 7. University of Utah, 8. David Geffen School of Medicine at UCLA, 9. Children’s Hospital of Philadelphia, 10. University of Texas Southwestern Medical Center, 11. AveXis, Inc., 12. AveXis, Inc., 13. AveXis, Inc., 14. AveXis, Inc., 15. AveXis, Inc., 16. AveXis, Inc., 17. AveXis, Inc., 18. AveXis, Inc., 19. AveXis, Inc., 20. Center for Gene Therapy, Nationwide Children’s Hospital

Background: SMA is a rapidly progressing disease causing loss of motor/respiratory functions due to survival motor neuron 1 gene (SMN1) deletion/mutation. Disease severity is modified by SMN2 copy number. AVXS-101 IT is a gene therapy that addresses the genetic root cause of SMA.

Objective: To assess the safety/tolerability, optimal dose, and efficacy of AVXS-101 IT in sitting but non-ambulatory patients with spinal muscular atrophy (SMA).

Approach: In STRONG (phase 1 study; NCT03381729), SMA patients (biallelic SMN1 loss, 3xSMN2) aged ≥6–<60 months who could sit but not stand/walk receive a one-time AVXS-101 IT dose (dose A: 6.0x10e13; B: 1.2x10e14; C: 2.4x10e14 vg).
Enrollment in dose B was complete following demonstration of acceptable safety in dose A and B. Primary endpoints: safety/tolerability, optimal dose, unsupported standing ≥3 seconds (≥6–<24 months), and change in Hammersmith Functional Motor Scale-Expanded (HFMSE) score from baseline (≥24–<60 months) at 12 months post-dose (dose B and C).

Results: As of 31 May 2019, 31 patients were enrolled (dose A, complete: n=3, ≥6–<24 months; dose B, complete: n=13, ≥6–<24 months; n=12, ≥24–<60 months; dose C, n=3). As of 8 March 2019 (n=30 patients), no fatal treatment-emergent adverse events (TEAEs) have occurred; 7 serious TEAEs occurred in 4 patients. As of 31 May 2019, HFMSE increased a mean 5.9 points from baseline at most recent visit in patients ≥24–<60 months (mean [range] duration of follow-up, 9.3 [7.2–11.9] months). Eighteen motor milestones were gained following treatment in patients ≥6–<24 months; 2 stood independently, 1 walked alone. In patients ≥24–<60 months, 3/12 (25%) gained motor milestones following treatment; 1 walked with assistance.

Conclusions: Interim data from STRONG demonstrate early signs of efficacy in sitting but non-ambulatory patients with SMA.