Motor function and independence
Risdiplam, non-ambulant, risdiplam, prolonged disease, later-onset SMA
DISEASE
Risdiplam treatment in a clinically heterogeneous population of children, teenagers, and adults with later-onset SMA and varying disease duration resulted in continued stabilization or improvement in motor function. Although analyses are exploratory, overall, the gains in motor function after 12 months of risdiplam treatment were maintained or improved upon up to month 24—confirming the benefit of longer-term risdiplam treatment.In patients with prolonged disease duration, the improvement with treatment is not expected to be evident in the short term, as it requires the activation of multiple compensatory reinnervation processes. Furthermore, hip contractures in non-ambulant patients with prolonged disease duration limit functional gains in tasks that require full hip extension. Thus, a goal of treatment is the long-term stability of specific functions, many of which involve the hands or upper extremities, which are important for the autonomy of non-ambulant patients. The progressive improvement on the RULM scale (1.91 at month 12, 2.06 at month 18, and 2.79 at month 24) following risdiplam treatment in this study exemplifies the impact of risdiplam on upper limb function. Increases in the caregiver-reported SMAIS-ULM total score (1.68 at month 12, 2.10 at month 18, and 2.73 at month 24; available for the full population), which is strongly correlated with the RULM [The trajectories of MFM32 and RULM total scores changed in patients who switched from placebo to risdiplam at month 12, while decline was observed from baseline to month 12 (when patients received placebo). A trend toward improvement or stabilization in motor function was observed from months 12 to 24 (12 months after the switch to risdiplam treatment).The external comparator analysis showed that risdiplam administration led to significant improvements in motor function at months 12 and 24 (Table In the comparison, analyses of MFM-derived total scores showed that risdiplam treatment in SUNFISH Part 2 led to an increase in mean score from baseline to month 24, which was significantly different from the progressive decline observed in the untreated external comparator. After 24 months of treatment, a higher proportion of individuals treated with risdiplam showed improvement or stabilization (≥ 3- or ≥ 0-point change, respectively) in MFM total score compared with the untreated external comparator. These results provide further confirmation of the longer-term efficacy of risdiplam in a broad population of patients with type 2 and non-ambulant type 3 SMA compared with untreated patients.Importantly, although risdiplam increases levels of functional SMN protein [