What are the benefits of switching from Spinraza (nusinersen) to Risdiplam (risdiplam)?

Switching from Spinraza to Risdiplam in Spinal Muscular Atrophy

Switching from Spinraza (nusinersen) to risdiplam is safe and maintains motor function stability, while offering the significant practical advantages of oral administration, broader systemic tissue penetration, and elimination of invasive intrathecal procedures. 1

Primary Benefits of Switching

Motor Function Stability

• Motor function remains largely stable after transitioning from nusinersen to risdiplam, with the greatest motor improvements typically occurring in the first year of nusinersen treatment before the switch 1
• In a single-center study of 44 patients (11 with SMA type 1,25 with type 2, and 8 with type 3), motor outcomes were maintained at 2 years post-switch 1
• The transition demonstrates a favorable safety profile with no significant motor deterioration 1

Respiratory and Bulbar Function Improvements

• Cough peak flow significantly improved in patients after switching to risdiplam compared to the nusinersen treatment period 1
• Two patients who were previously tube-fed achieved some oral feeding capability, and two became exclusively orally fed after switching to risdiplam 1
• Hospitalization rates remained equivalent between nusinersen and risdiplam treatment periods 1

Administration and Accessibility Advantages

• Risdiplam is the first and only oral medication approved for SMA, eliminating the need for repeated intrathecal injections required with nusinersen 2
• The oral route provides a non-invasive approach particularly beneficial in infants and young children 2
• Risdiplam provides stronger systemic tissue penetration than intrathecal therapies, reaching peripheral tissues more effectively 2
• The medication can be administered at home, reducing the burden of frequent hospital visits for intrathecal procedures 3

Safety Profile

Established Safety Data

• The safety profile of risdiplam in real-world settings mirrors clinical trial data with no new safety concerns identified 3
• In the UK Early Access to Medicines Scheme involving 92 pediatric patients, 60 adverse events were reported in 34 patients, with 38/60 considered unrelated to risdiplam 3
• The most common adverse events were respiratory tract infections and gastrointestinal disturbances 3

Switching Safety

• Transitioning from nusinersen to risdiplam is associated with a favorable safety profile across all SMA types 1
• Patients previously treated with nusinersen who switched to risdiplam showed no unexpected safety signals 3
• The switch can be performed safely even in patients who have been on nusinersen for extended periods 1

Long-Term Comparative Outcomes

Superior Efficacy Metrics

• Children with type 1 SMA treated with risdiplam demonstrated a 78% reduction in the rate of death and an 81% reduction in death or permanent ventilation compared to nusinersen in matched indirect comparison analysis 4
• Risdiplam-treated patients showed a 57% reduction in serious adverse events compared to nusinersen 4
• A 45% higher rate of achieving motor milestone responses and 186% higher rate of achieving ≥4-point improvement in neuromuscular testing was observed with risdiplam 4

Clinical Considerations for Switching

Patient Selection

• Patients experiencing difficulties with intrathecal administration (anatomical challenges, posterior spinal fusion, anxiety) are ideal candidates for switching 1, 3
• Those requiring broader systemic tissue coverage benefit from risdiplam's oral bioavailability 2
• Patients aged 2 months and older across all SMA types (1,2, and 3) are appropriate candidates 3

Impact of Spinal Surgery

• Over half (57%) of patients in the transition study had posterior spinal fusion surgery, which significantly impacted motor and respiratory outcomes 1
• The negative impact of spinal fusion was slightly less pronounced in the risdiplam group compared to the nusinersen group 1

Common Pitfalls and How to Avoid Them

Expectation Management

• Do not expect additional motor gains immediately after switching—the primary benefit is maintaining stability while gaining practical advantages 1
• The most significant motor improvements occur in treatment-naïve patients during the first year of any disease-modifying therapy 1

Monitoring Requirements

• Continue regular assessment of motor, pulmonary, and bulbar function after transition 1
• Monitor for respiratory tract infections and gastrointestinal symptoms, the most common adverse events 3
• Assess cough effectiveness and swallowing function, as these may show improvement 1

Timing Considerations

• The switch can be performed at any point during nusinersen treatment without a washout period 1
• Patients should not delay switching if practical benefits (avoiding intrathecal procedures, home administration) would significantly improve quality of life 2