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.