A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND)

Key Inclusion Criteria:

• Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) genedeletion or mutation or compound heterozygous mutation.

• Diagnosis of later-onset SMA with symptom onset at age >6 months.

• Aged ≥15 to ≤50 years at the time of informed consent

• Body weight >20 kg.

• Received oral risdiplam per the approved label or per the managed access program asfollows

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 monthsand must have been on risdiplam for ≥12 months before enrollment.

• Able to perform the age-appropriate functional assessments in the study.

• RULM entry item A score ≥3.

• RULM total score ≥5 and ≤30 at Screening.

• Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independentlywithout support.

• Willing to stop risdiplam treatment.

• Willing and able to start treatment with HD nusinersen.

Key Exclusion Criteria:

• Any major illness within 1 month before the screening examination or within 1 weekprior to Screening and up to first dose administration.

• Presence of an untreated or inadequately treated active infection requiring systemicantiviral or antimicrobial therapy at any time during the Screening Period.

• Presence of an implanted shunt for the drainage of CSF or of an implanted centralnervous system catheter.

• Permanent tracheostomy or permanent ventilation at Screening.

• The medical necessity, as defined by the Investigator, for noninvasive ventilationsuch as bilevel positive airway pressure or continuous positive airway pressureoutside of regular sleep hours for any reason other than proactive SMA management,at Screening.

• History of bacterial meningitis, viral encephalitis, or hydrocephalus.

• Ongoing medical condition that according to the Investigator would interfere withthe conduct and assessments of the study. An example is a medical disability (e.g.,wasting or cachexia, severe anemia, and respiratory parameters) that would interferewith the assessment of safety or would compromise the ability of the participant toundergo study procedures.

• Participants who are pregnant or currently breastfeeding and those intending tobecome pregnant during the study.

• Treatment with an investigational drug, biological agent, or device within 30 daysor 5 half-lives of the agent, whichever is longer, prior to Screening or anytimeduring the study; any prior or current treatment with gene therapy for the treatmentof SMA.

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