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250 AVXS-101 phase 3 study in spinal muscular atrophy type 1
  1. John W Day1,
  2. Claudia A Chiriboga2,
  3. Thomas O Crawford3,
  4. Basil T Darras4,
  5. Richard S Finkel5,
  6. Anne M Connolly6,7,8,9,
  7. Susan T Iannaccone10,
  8. Nancy L Kuntz11,
  9. Loren DM Peña12,
  10. Meredith Schultz13,
  11. Perry B Shieh14,
  12. Edward C Smith15,
  13. Imran Kausar13,
  14. Douglas E Feltner13,
  15. Francis G Ogrinc13,
  16. Haojun Ouyang13,
  17. Thomas A Macek13,
  18. Elaine Kernbauer13,
  19. Lynlee M Muehring13,
  20. James L’Italien13,
  21. Douglas M Sproule13,
  22. Brian K Kaspar13,
  23. Jerry R Mendell7,8,9
  1. 1Department of Neurology, Stanford University Medical Center, Stanford, CA, USA
  2. 2Division of Pediatric Neurology, Columbia University Medical Center, New York, NY, USA
  3. 3Department of Neurology, Johns Hopkins Medicine, Baltimore, MD, USA
  4. 4Department of Neurology, Boston Children’s Hospital, Boston, MA, USA
  5. 5Division of Neurology, Department of Pediatrics, Nemours Children’s Hospital, Orlando, FL, USA
  6. 6Department of Neurology, Nationwide Children’s Hospital, Columbus, OH, USA
  7. 7Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA
  8. 8Department of Pediatrics, Ohio State University, Columbus, OH, USA
  9. 9Department of Neurology, Ohio State University, Columbus, OH, USA
  10. 10Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
  11. 11Division of Neurology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA
  12. 12Division of Human Genetics, Cincinnati Children’s Hospital and University of Cincinnati College of Medicine, Cincinnati, OH, USA
  13. 13AveXis, Inc., Bannockburn, IL, USA
  14. 14Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
  15. 15Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA


Background Onasemnogene abeparvovec (AVXS-101), a one-time intravenous gene-replacement therapy, treats the genetic root cause of spinal muscular atrophy (SMA). In the phase 1 study, AVXS-101 dramatically improved survival, motor function, and motor milestone achievement in SMA type 1 (SMA1) patients.

Methods STR1VE is a phase 3, multicenter, open-label study (NCT03306277) in SMA1 patients <6 months (bi-allelic survival motor neuron 1 gene [SMN1] mutations/deletions, 2 SMN2 copies). Primary outcomes are independent sitting ≥30 seconds at 18 months of age, and survival (no death/permanent ventilation) at 14 months. Secondary outcomes include ability to thrive and ventilatory support at 18 months. Exploratory outcomes include CHOP-INTEND and Bayley-III.

Results Enrollment is complete (22 patients dosed). Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support. Mean baseline CHOP-INTEND: 32.6 (17.0–52.0) points; increased by 6.9 (-4.0–16.0), 9.2 (0–18.0), and 11.7 (-3.0–23.0) points at 1, 2, and 3 months; independent sitting: 11/22 patients; survival at 13.6 months: 13/15 (87%) (8 March 2019 datacut).

Conclusions Preliminary data from the AVXS-101 phase 3 study show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.

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