What is the preferred treatment for adults with Spinal Muscular Atrophy (SMA) type 3, comparing risdiplam (Risdiplam) to Spinraza (Nusinersen)?

Treatment Comparison: Risdiplam vs Spinraza for Adults with SMA Type 3

For adults with SMA type 3, risdiplam offers comparable motor function improvements to Spinraza (nusinersen) with the significant advantage of oral administration, making it the preferred choice for most patients, particularly those who cannot tolerate or access intrathecal injections.

Key Efficacy Differences

Risdiplam Performance in Adults

• Motor function improvements are clinically meaningful: In adult SMA type 2 and 3 patients, risdiplam demonstrated statistically significant improvements in multiple motor scales including Hammersmith Functional Motor Scale-Expanded (mean difference 1.5), Revised Upper Limb Module (mean difference 1.6), and Motor Function Measurement-32 (mean difference 2.7) over 28.5 months 1
• High responder rate: 82% of adult patients achieved clinically meaningful improvement in at least one motor scale, with improvements occurring earlier in type 3 patients 1
• Sustained benefits: Motor improvements were maintained or further improved at 24 months, with 32% showing improvement (≥3 point change in MFM32) and 58% demonstrating stabilization 2
• Treatment-naive patients respond well: 93% of treatment-naive adult patients showed positive outcomes with risdiplam 1

Comparative Motor Outcomes

• MFM32 sensitivity: The Motor Function Measure-32 proved more sensitive than HFMSE in detecting treatment-induced changes in adults, showing improvements ranging from +2.16% to +7.29% in responsive patients 3
• Subdomain improvements: Domain D3 (distal motor function) improved in 66.6% of patients, indicating benefits in hand dexterity and fine motor skills 3

Administration and Practical Advantages

Risdiplam Benefits

• Oral administration: Once-daily oral dosing (5 mg) eliminates the need for repeated intrathecal injections 3, 1
• Outpatient feasibility: Drug administration and patient management proved feasible and safe in outpatient settings 1
• No procedural complications: Avoids risks associated with lumbar punctures and intrathecal administration

Spinraza Limitations

• Intrathecal requirement: Requires repeated lumbar punctures for drug delivery, which can be challenging in adults with spinal deformities or fusion
• Procedural burden: More invasive administration route may limit accessibility and patient acceptance

Safety and Tolerability Profile

Risdiplam Safety

• Excellent tolerability: 57% of patients reported no adverse events, and none discontinued treatment over 30 months 1
• Mild side effects: When present, adverse effects were mild and decreased over time 3
• No new safety signals: Real-world data has not identified any unexpected safety concerns 4
• Favorable benefit-risk balance: Maintained across up to 2 years of treatment 5

Switching from Spinraza

• Maintained function: Patients previously treated with Spinraza who switched to risdiplam due to side effects maintained their pre-risdiplam motor scores, indicating no loss of benefit with transition 3

Patient-Reported Outcomes

Functional Improvements Beyond Motor Scales

• Bulbar function: Majority of patients with bulbar impairment experienced improvements in voice intelligibility and swallowing 3, 4
• Respiratory benefits: Improvements in breath fatigue reported, with respiratory function tests remaining stable 3, 1
• Quality of life: All patients reported increased quality of life with treatment 4
• Unexpected benefits: One-third of patients experienced weight gain with improved appetite and digestion, suggesting systemic therapeutic effects 4

Clinical Decision Algorithm

Choose Risdiplam When:

• Patient is treatment-naive with SMA type 3
• Patient has difficulty with intrathecal access (spinal fusion, scoliosis)
• Patient prefers oral administration
• Outpatient management is preferred
• Patient previously experienced side effects with Spinraza

Consider Continuing Spinraza When:

• Patient is already stable and responding well to Spinraza
• Patient has established tolerance to intrathecal administration
• No access issues with lumbar puncture

Monitoring Strategy

• Baseline assessment: Establish MFM32 scores as primary outcome measure, as it is more sensitive than HFMSE in adults 3
• Follow-up intervals: Assess motor function at 6,12,18,24, and 30 months 1
• Multisystem monitoring: Track bulbar function, respiratory parameters, and patient-reported outcomes given systemic nature of therapy 4
• Early response indicators: Type 3 patients typically show clinically meaningful improvements earlier than type 2 patients 1

Treatment Duration Considerations

• Long-term efficacy: Benefits are sustained and often improve further with continued treatment beyond 12 months 2
• Stabilization value: Even patients showing stabilization rather than improvement benefit from continued treatment, as natural history would predict decline 2
• Treatment persistence: The oral route and favorable tolerability support long-term adherence 1