Onasemnogene Abeparvovec-xioi Gene Therapy for Spinal Muscular Atrophy Type 1 (SMA1): Phase 3 US Study (STR1VE) Update


Clinical Trials

Poster Number: 40


John Day, MD, PhD, Claudia A. Chiriboga, Thomas Crawford, MD, Basil Darras, MD, Richard Finkel, MD, Anne Connolly, MD, Susan T. Iannaccone, MD, Nancy Kuntz, MD, PhD, Loren D.M. Peña, Perry Shieh, MD, PhD, Edward C. Smith, MD, Jennifer M. Kwon, MD, Craig Zaidman, MD, Meredith Schultz, Douglas E. Feltner, Sitra Tauscher-Wisniewski, MD, Francis G. Ogrinc, Peter Thomasma, Haojun Ouyang, Thomas A. Macek, Elaine Kernbauer, Douglas M. Sproule, Jerry R. Mendell


1. Stanford, 2. Columbia University Irving Medical Center, 3. The Johns Hopkins University School of Medicine, 4. Boston Children's Hospital, 5. Nemours Children’s Hospital, University of Central Florida College of Medicine, 6. Nationwide Children's Hospital, 7. University of Texas Southwestern Medical Center, 8. Lurie Children's Hospital - Chicago, 9. Division of Human Genetics, Cincinnati Children’s Hospital, 10. David Geffen School of Medicine at UCLA, 11. Department of Pediatrics, Duke University School of Medicine, 12. University of Wisconsin School of Medicine and Public Health, 13. Washington University in Saint Louis, 14. AveXis, Inc., 15. AveXis, Inc., 16. AveXis, Inc., 17. AveXis, Inc., 18. AveXis, Inc., 19. AveXis, Inc., 20. AveXis, Inc., 21. AveXis, Inc., 22. AveXis, Inc., 23. Center for Gene Therapy, Nationwide Children’s Hospital

Background: SMA1 is caused by functional loss of SMN1, and typically results in death/permanent ventilation by 2 years if untreated. Onasemnogene abeparvovec-xioi (formerly AVXS-101), a one-time, AAV9-based, intravenous gene therapy, addresses the genetic root cause of SMA and is designed for sustained SMN protein expression in neurons.
Objective: Assess preliminary data from the phase 3 STR1VE (NCT03306277) study evaluating efficacy/safety of onasemnogene abeparvovec in SMA1 patients (pts).
Methods: STR1VE is a multicenter, open-label, single-arm, single-dose study in symptomatic SMA1 pts aged <6 months (biallelic SMN1 mutations, 1–2 SMN2 copies [1–2xSMN2]) conducted in the United States. Outcomes: independent sitting ≥30 seconds at 18 months, survival (no death/permanent ventilation) at 14 months, and motor function improvements (Bayley-III, CHOP INTEND). Safety outcomes: unanticipated treatment-related toxicity of grade ≥3 based on CTCAE.
Results: As of 31 May 2019, enrollment is complete (N=22; 2xSMN2; 10 male, 12 female). Mean age (range) at dosing: 3.7 (0.5–5.9) months. Of 19 pts who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation (death unrelated to treatment, n=1; respiratory endpoint prior to withdrawal of consent, n=1) compared with 25% survival in untreated natural history. Mean (range) baseline CHOP INTEND score was 32 (18–52) and increased 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. 11/22 (50%) pts sat independently ≥30 sec (mean of 8.2 months post-treatment); 5/6 (83%) pts ≥18 months old sat independently ≥30 sec (co-primary endpoint). As of 8 March 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.
Conclusions: Interim data from the ongoing STR1VE study suggest that a one-time intravenous dose of onasemnogene abeparvovec provides benefit in pts with SMA1. Updated data from STR1VE will be presented.