Spinal Muscular Atrophy

To collect long-term follow-up safety and efficacy data in patients with spinal muscular atrophy (SMA) Type 1, Type 2 or Type 3 who were treated with AVXS-101 in an AVXS-101 clinical trial, including but not limited to AVXS-101-CL-102 (Phase 1), AVXS-101-CL-302 (Phase 3), AVXS-101-CL-303 (Phase 3), AVXS-101-CL-304 (Phase 3) or AVXS-101-CL-306 (Phase 3). In addition; patients treated with AVXS-101 (intravenous [IV] or intrathecal [IT] administration) in future parent studies may be enrolled.

AVXS-101

Survival Motor Neuron Gene delivered by Self‐Complementary Adeno-Associated Virus Serotype 9 ( scAAV

Vial for injection

1.1 X 1014 vg/kg

• Number of participants who reach developmental milestones [ Time Frame: Up to 5 years ]
Assessed via the developmental milestone checklist, formed of 10 yes/no questions. The developmental milestones are: head control, sitting with support, sitting without support, sitting without support for 30 seconds, hands-and-knees crawling, pulls to stand, standing with assistance, walking with assistance, standing alone and walking alone.
• Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) score [ Time Frame: Up to 2 years ]
The HFMSE was devised for use in children with SMA Type 2 and Type 3, to give objective information on motor ability and clinical progression. The HFMSE is formed of 33 assessments rated from 0 (unable to perform functional task) to 2 (able to perform functional task unassisted). Higher scores indicated higher levels of motor ability.
• Number of participants who experience a clinically significant change from baseline in pulmonary assessment results [ Time Frame: Up to 15 years ]
Participants will receive pulmonary assessments by a pulmonologist or appropriate clinician. Respiratory device data will be reviewed for participants receiving non-invasive ventilatory support.
• Number of participants who experience swallowing dysfunction [ Time Frame: Up to 5 years ]
Assessed via the swallowing function questionnaire, formed of 4 yes/ no questions and 1 body weight question.
• Number of participants who experience a clinically significant change from baseline in physical examination findings [ Time Frame: Up to 5 years ]
The physical examination includes review of the following systems: head, ears, eyes, nose and throat, lungs/thorax, cardiovascular, abdomen, musculoskeletal, neurologic, dermatologic, lymphatic, and genitourinary. In addition, visual inspection of the spine, back, shoulders, and hips looking for spinal curvature and asymmetry will be carried out. Joints will be assessed for loss of mobility and contractures.
• Number of participants who experience a clinically significant change from baseline in vital signs measurements [ Time Frame: Up to 5 years ]
Vital sign measurements will include blood pressure, respiratory rate, pulse, axillary temperature, and pulse oximetry.
• Change from baseline in height measurements [ Time Frame: Up to 5 years ]
• Change from baseline in weight measurements [ Time Frame: Up to 5 years ]
• Number of participants who experience a clinically significant change from baseline in clinical laboratory assessments [ Time Frame: Up to 5 years ]
Blood samples will be collected for hematology (including complete blood cell count) and chemistry.
• Number of participants who experience a clinically significant change from baseline in cardiac assessments [ Time Frame: Up to 5 years ]
Cardiac assessments will include a 12-lead electrocardiogram, transthoracic echocardiogram and 24-hour Holter monitor.
• Number of participants who experience a clinically significant change from baseline in observational phase questionnaire results [ Time Frame: Year 6 to Year 15 ]
The observational phase questionnaire includes 7 yes/no questions. Observation categories include: adverse events, hospitalizations, concomitant medications, ventilatory support and feeding support.
• Number of participants who experience at least one serious adverse event (SAE) [ Time Frame: Up to 15 years ]
An adverse event (AE) is defined as the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered casually related to the product. An SAE is defined as an AE occurring during any study phase that fulfills one or more of the following criteria:
o Results in death
o Is immediately life-threatening
o Requires in-patient hospitalization or prolongation of existing hospitalization
o Results in persistent or significant disability or incapacity
o Results in a congenital abnormality or birth defect
o Is an important medical event that may jeopardize the patient/subject or may require medical intervention to prevent one of the outcomes listed above.
• Number of participants who experience at least one adverse event of special interest (AESI) [ Time Frame: Up to 15 years ]
An AESI is defined as an AE occurring during any study phase that fulfills one of the following criteria:
o Liver function enzyme elevations 2 × the upper limit of normal
o New neoplasms or malignancies
o New incidence or exacerbation of a pre-existing neurologic disorder
o New incidence or exacerbation of a prior rheumatologic or other autoimmune
disorder
o New incidence of hematologic disorder.

Inclusion Criteria:
• Participants with SMA (with 1, 2 or 3 copies of SMN2) who received onasemnogene abeparvovec-xioi gene replacement therapy in an AveXis clinical study
• Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule

Exclusion Criteria:
• Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study