AveXis Managed Access Program Cohort for Access to AVXS-101

The purpose of this Cohort Treatment Protocol will allow access to AVXS-101 for eligible patients diagnosed with SMA.

The purpose of this Cohort Treatment Protocol will allow access to AVXS-101 for eligible patients diagnosed with SMA.

The requesting Physician submits a request for access to drug (often referred to as Compassionate Use) to AveXis which is reviewed and approved by the medical team experienced with the drug and indication. The requesting Physician should refer to the latest Investigator's Brochure (IB) or approved label for overview of drug including: nonclinical and clinical experience, risk and benefits.

Eligibility Criteria:
Inclusion Criteria:

1. Patients with SMA must satisfy both a. and b. of the following specified criteria:

   1. Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 1, 2, or 3 copies of SMN2.
   2. Either patients with onset of symptoms prior to \< 6 months (\< 180 days) of age or pre-symptomatic patients, less than 6 months of age, with 1, 2, or 3 copies of SMN2 who are not excluded for other reasons.
2. Weight ≥ 2.6 kg to ≤ 13.5 kg at dosing.
3. Patients must have a pre-treatment swallowing evaluation test performed prior to administration of AVXS-101.
4. Patients must have a formal pulmonary evaluation including documentation of non-invasive ventilatory use prior to administration of AVXS-101. Ventilation should be actively managed by an appropriately trained specialist per the published standard of care.
5. Up-to-date on childhood vaccinations. Seasonal vaccinations and palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections have been administered as recommended by the American Academy of Pediatrics.
6. Parent(s)/legal guardian(s) willing and able to complete the informed consent process and comply with study procedures and visit schedule.

Exclusion Criteria:

1. Tracheostomy.
2. Contraindication to receiving glucocorticosteroids or their excipients.
3. Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer \> 1:50 (or any value reported as elevated for the laboratory) as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. Should a potential patient demonstrate AntiAAV9 antibody titer \> 1:50, he or she may be retested and will be eligible to participate if the AntiAAV9 antibody titer upon retesting is ≤ 1:50.
4. Clinically significant abnormal laboratory values for troponin-I, and platelets. ALT, AST, bilirubin or gamma glutamyl transferase (GGT) \> 2 x the upper limit of normal (ULN) prior to gene replacement therapy that in the judgment of the Treating Physician or AveXis would create too great a risk for the patient to be treated with AVXS-101 or prophylactic prednisolone. Note: Elevated bilirubin \> 2 x ULN if associated with neonatal jaundice is not considered exclusionary.
5. Medical conditions, diagnoses (especially cardiac), or on concurrent medications prior to gene replacement therapy that in the judgment of the treating physician or sponsor would create too great a risk for the patient to be treated with AVXS-101 or prophylactic prednisolone.
6. Participation or expected participation in current treatment clinical study (with the exception of observational cohort studies or non-interventional studies) for an unapproved investigational agent.
7. Parent(s)/legal guardian(s) unwilling to keep study results/observations confidential or to refrain from posting confidential study results/observations on social media sites.
8. Parent(s)/legal guardian(s) refuses to sign consent form.