A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam

Key Inclusion Criteria:

1. Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
2. Diagnosis of later-onset SMA with symptom onset at age >6 months.
3. Aged ≥15 to ≤50 years at the time of informed consent
4. Body weight >20 kg.

Received oral risdiplam per the approved label or per the managed access program as follows

1. Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months before enrollment.
2. Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and must have been on risdiplam for ≥12 months before enrollment.
3. Able to perform the age-appropriate functional assessments in the study.
4. RULM entry item A score ≥3.
5. RULM total score ≥5 and ≤30 at Screening.
6. Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
7. Willing to stop risdiplam treatment.
8. Willing and able to start treatment with HD nusinersen.

Key Exclusion Criteria:

1. Any major illness within 1 month before the screening examination or within 1 week prior to Screening and up to first dose administration.
2. Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
3. Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
4. Permanent tracheostomy or permanent ventilation at Screening.
5. The medical necessity, as defined by the Investigator, for noninvasive ventilation such as bilevel positive airway pressure or continuous positive airway pressure outside of regular sleep hours for any reason other than proactive SMA management, at Screening.
6. History of bacterial meningitis, viral encephalitis, or hydrocephalus.
7. Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
8. Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
9. Treatment with an investigational drug, biological agent, or device within 30 days or 5 halflives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.