Risdiplam in types 2 and 3 spinal muscular atrophy: A randomised, placebo‐controlled, dose‐finding trial followed by 24 months of treatment
Key result
Risdiplam treatment produced a dose-dependent, median twofold increase in blood SMN protein within 4 weeks that was sustained over 24 months.
Why the study?
Spinal muscular atrophy is caused by reduced survival of motor neuron (SMN) protein levels, and the appropriate dose of the SMN2 pre-mRNA splicing modifier risdiplam needed to be identified for a pivotal trial.
Does risdiplam increase functional SMN protein and demonstrate safety in individuals with types 2 and 3 spinal muscular atrophy?
Population
51 individuals with types 2 and 3 SMA aged 2-25 years
Comparison
Risdiplam vs placebo at escalating dose levels
Design
Randomized (2:1), double-blind, placebo-controlled dose-finding trial
Follow-up
24 months
Authors
Discussion
Loading...
Member takes
Implication
Supports risdiplam dose selection for pivotal SMA trials; extends pharmacodynamic data for SMN modulators in types 2/3 disease.
Study Design
Type
RCT (n=51)
Blinding
double-blind
Randomization
2:1
Structured PICO
Does risdiplam increase functional SMN protein and demonstrate safety in individuals with types 2 and 3 spinal muscular atrophy?
P
Population
51 individuals aged 2-25 years with types 2 and 3 spinal muscular atrophy, randomized to risdiplam or placebo for a minimum 12-week double-blind period followed by 24 months of treatment.
I
Intervention
Risdiplam orally administered at escalating dose levels for a minimum 12-week period, followed by treatment for 24 months
C
Comparator
Placebo for a minimum 12-week period
O
Outcome
Dose selection based on safety, tolerability, pharmacokinetic, and pharmacodynamic data (blood SMN protein)surrogate
Risdiplam safely increased blood SMN protein levels twofold in patients with types 2 and 3 SMA, establishing the dose for the pivotal phase 2 trial.
Cite This Study
Mercuri et al. (2022) conducted an RCT in types 2 and 3 spinal muscular atrophy (n=51). Risdiplam vs. Placebo was evaluated on Blood SMN protein levels. Risdiplam treatment produced a dose-dependent, median twofold increase in blood SMN protein within 4 weeks that was sustained over 24 months.