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AVXS-101 Phase 1 Gene Therapy Clinical Trial in SMA Type 1: Continued Event-Free Survival, Achievement of Developmental Milestones, and Continued Respiratory and Nutritional Support Independence
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A6328 - AVXS-101 Phase 1 Gene Therapy Clinical Trial in SMA Type 1: Continued Event-Free Survival, Achievement of Developmental Milestones, and Continued Respiratory and Nutritional Support Independence
Author Block: R. Shell1, S. Al-Zaidy1, K. Kotha1, W. Arnold2, L. Rodino-Klapac1, T. Prior2, L. Lowes1, L. Alfano1, K. Berry1, K. Church1, J. Kissel2, S. Nagendran3, J. L'Italien3, D. Sproule3, C. Wells3, A. Burghes2, K. Foust3, K. Meyer1, S. Likhite1, B. Kaspar3, J. Mendell1; 1Nationwide Children Hosp, Columbus, OH, United States, 2Ohio State University, Columbus, OH, United States, 3AveXis, Inc., Bannockburn, IL, United States.
We previously reported that all 15 SMA1 patients receiving a one-time intravenous dose of AVXS-101 survived to 13.6 months without permanent-ventilation (20January2017), an age that natural history indicates only 25% of SMA1 children will reach free of permanent-ventilation (i.e. event-free). Moreover, those receiving the proposed therapeutic dose required less supportive care and achieved major motor milestone unprecedented in the natural history. Here we report that all 15 patients continue to survive, reach additional motor milestones and those that were independent of respiratory/nutritional support continue independent of such intervention at ≥20 months of age. In this study, 15 patients with SMA1 (with 2xSMN2 copies) were enrolled. Patients received an intravenous dose of AVXS-101 at low-dose (Cohort 1, n=3) or proposed therapeutic dose (Cohort 2, n=12). The primary objective was safety and secondary objectives included survival (avoidance of death/event-free) and sitting unassisted. No new treatment-related AEs were reported and all patients were alive at ≥20 months event-free (7August2017). Patients in Cohort-2 continued to demonstrate improvements in motor milestone since 20January2017: 4 additional patients achieved sitting unassisted for ≥30 seconds; thus, 9/12 patients have achieved/maintained sitting unassisted for ≥30 seconds. Eleven of 12 patients have sustained CHOP-INTEND scores >40 for a mean of 18.8 months. Patients who were free of respiratory or nutritional support at 20January2017 continue without the need for supportive care.Patients in this Phase 1 study who received a one-time intravenous dose of AVXS-101 continue to survive, improve in motor ability, maintain bulbar muscle function, and respiratory muscle function as demonstrated by the decreased need for supportive care. Moreover, none of the patients have needed tracheostomy and returned to baseline after a course of respiratory illness, which typically results in permanent invasive ventilation or death in untreated SMA1 patients.
Author Block: R. Shell1, S. Al-Zaidy1, K. Kotha1, W. Arnold2, L. Rodino-Klapac1, T. Prior2, L. Lowes1, L. Alfano1, K. Berry1, K. Church1, J. Kissel2, S. Nagendran3, J. L'Italien3, D. Sproule3, C. Wells3, A. Burghes2, K. Foust3, K. Meyer1, S. Likhite1, B. Kaspar3, J. Mendell1; 1Nationwide Children Hosp, Columbus, OH, United States, 2Ohio State University, Columbus, OH, United States, 3AveXis, Inc., Bannockburn, IL, United States.
We previously reported that all 15 SMA1 patients receiving a one-time intravenous dose of AVXS-101 survived to 13.6 months without permanent-ventilation (20January2017), an age that natural history indicates only 25% of SMA1 children will reach free of permanent-ventilation (i.e. event-free). Moreover, those receiving the proposed therapeutic dose required less supportive care and achieved major motor milestone unprecedented in the natural history. Here we report that all 15 patients continue to survive, reach additional motor milestones and those that were independent of respiratory/nutritional support continue independent of such intervention at ≥20 months of age. In this study, 15 patients with SMA1 (with 2xSMN2 copies) were enrolled. Patients received an intravenous dose of AVXS-101 at low-dose (Cohort 1, n=3) or proposed therapeutic dose (Cohort 2, n=12). The primary objective was safety and secondary objectives included survival (avoidance of death/event-free) and sitting unassisted. No new treatment-related AEs were reported and all patients were alive at ≥20 months event-free (7August2017). Patients in Cohort-2 continued to demonstrate improvements in motor milestone since 20January2017: 4 additional patients achieved sitting unassisted for ≥30 seconds; thus, 9/12 patients have achieved/maintained sitting unassisted for ≥30 seconds. Eleven of 12 patients have sustained CHOP-INTEND scores >40 for a mean of 18.8 months. Patients who were free of respiratory or nutritional support at 20January2017 continue without the need for supportive care.Patients in this Phase 1 study who received a one-time intravenous dose of AVXS-101 continue to survive, improve in motor ability, maintain bulbar muscle function, and respiratory muscle function as demonstrated by the decreased need for supportive care. Moreover, none of the patients have needed tracheostomy and returned to baseline after a course of respiratory illness, which typically results in permanent invasive ventilation or death in untreated SMA1 patients.
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