AVXS-101 in infants with Pre-symptomatic Spinal Muscular Atrophy
Research type
Research Study
Full title
A Global Study of a Single, One-Time Dose of AVXS-101 Delivered to Infants with Genetically Diagnosed and Pre-symptomatic Spinal Muscular Atrophy with Multiple Copies of SMN2
IRAS ID
246290
Contact name
Francesco Muntoni
Contact email
Sponsor organisation
AveXis, Inc
Eudract number
2017-004087-35
Duration of Study in the UK
4 years, 6 months, 1 days
Research summary
Research Summary
Spinal muscular atrophy (SMA) is a rare genetic disorder. Symptoms of SMA occur when the Survival Motor Neuron (SMN) protein (a molecule in the body that helps to build, maintain and replace tissues in your body) is missing in the spinal cord and motor nerves. Without SMN, the nerve control will worsen and cause muscle weakness as well as swallowing/breathing problems and other complications. Approximately 1 in 10,000 babies are affected, and SMA has limited treatment options. Disease severity correlates with SMN levels, emphasising the potential benefit for SMN treatment strategy.
This study is a phase 3, open-label, single-arm study of a one-time dose of AVXS-101. AVXS-101 is a gene replacement therapy which contains the SMN gene. AVXS-101 will be delivered into the body using a modified virus called adeno-associated virus (AAV) as it can cross the “blood-brain barrier” (a tight barrier separating blood vessels from the spinal cord and brain), allowing delivery to the place where neurons are affected the most by the faulty SMN1 gene.
The diagnosis of SMA is based on the onset of clinical symptoms and genetic testing confirming the loss of SMN1 gene/the number of SMN2 back up genes. The number of copies of SMN2 backup genes helps to predict the severity of the disease. The study will therefore enrol 15 patients with 2 copies; 12 patients with 3 copies and at least 17 patients with 4 copies. Patients in all three cohorts must be more than 6 weeks of age at the time of gene replacement therapy (Day 1) and will be recruited into 24 study centres around the world.
Depending on the number of SMN2 copies, duration in the study will range from 18 to 36 months. The study includes a screening period, a gene replacement therapy period, and a follow-up period.
Summary of Results
From Cohort 1, all 14 patients achieved the milestone ‘sits without support’ at any visit. Eleven patients achieved this milestone within the normal developmental window. All 14 patients survived event free to ≥14 months of age without permanent ventilation. Thirteen out of 14 patients maintained weight without the need for non-oral/mechanical feeding support at all visits up to 18 months of age.
From Cohort 2, all 15 patients achieved the milestone ‘stands alone’. Fourteen patients achieved this milestone within the normal developmental window. Fourteen out of 15 patients achieved the milestone ‘walks alone’ at any visit up to 24 months of age. Eleven out of 15 patients achieved this milestone within the normal developmental window.
Adverse Events (AEs) are undesirable events that occur at any time during the study, whether or not considered related to study treatment. Serious Adverse Events (SAEs) are those that lead to death, or are life-threatening or disabling, or require or prolong hospitalisation.
Treatment emergent adverse events (TEAE) are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.
While all patients in Cohort 1 and Cohort 2 had at least 1 TEAE, the majority of AEs were mild or moderate in intensity, and non-serious.
Ten patients in Cohort 1 and 8 patients in Cohort 2 had at least 1 TEAE that was considered by the Investigator to be possibly, probably, or definitely related to AVXS-101. The most frequent related TEAE in both cohorts was increased aspartate aminotransferase (a chemical found in the liver and muscles; high levels could indicate liver damage).
Few patients (5 in Cohort 1, 3 in Cohort 2) experienced SAEs, none of which were considered related to AVXS-101 by the Investigator.
No patient died during this study, and none discontinued the study.REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/0983
Date of REC Opinion
20 Aug 2018
REC opinion
Further Information Favourable Opinion