Table 2.
Summary of clinical trials compared in the SMA MAICs
| Infantile-onset SMA | Later-onset SMA | |||||
|---|---|---|---|---|---|---|
| ENDEAR [35]/SHINE [36] | STR1VE-US [37] | START [38] | FIREFISH [39] | CHERISH [40] | SUNFISH Part 2 [41] | |
| Study design |
ENDEAR: randomized, double-blind, sham-procedure controlled study SHINE: open-label, 5-year extension study of ENDEAR participants |
Open-label, single-arm study | Open-label, single-arm study | Open-label study with two parts: (1) dose finding and (2) confirmatory, single-arm | Randomized, double-blind, sham-controlled study | Randomized, double-blind, placebo-controlled study |
| Treatment groups | Nusinersen vs. sham-procedure | Onasemnogene abeparvovec | Onasemnogene abeparvovec | Risdiplam | Nusinersen vs. sham-procedure | Risdiplam vs. placebo |
| Sample size | Nusinersen (n = 81)a, sham (n = 41) | n = 22 | n = 15 | n = 62 | Nusinersen (n = 84), sham (n = 42) | Risdiplam (n = 120), placebo (n = 60) |
| Key inclusion criteria |
Age ≤ 7 months at screening 2 SMN2 copies |
Age < 6 months at time of dosing 2 SMN2 copiesb |
Age at dosing < 9 months for first 9 patients; age at dosing < 6 months for the last six patients 2 SMN2 copies |
Age ≤ 7 months at enrollment 2 SMN2 copies |
Age 2–12 years at screening Can sit independently, but not walk independently |
Age 2–25 years at screening Type 2 or 3 SMA; non-ambulant but can sit independently |
| Key exclusion criteria | Hypoxemia at screening |
Tracheostomy or non-invasive ventilatory support ≥ 6 h per day over the 7 days prior to screening Pulse oximetry < 96% saturation at screening Signs of aspiration |
Invasive ventilatory support or pulse oximetry < 95% saturation Signs of aspiration |
Hospitalization for pulmonary event within the last 2 months Invasive ventilation or tracheostomy Awake non-invasive ventilation or with awake hypoxemia with or without ventilator support History of respiratory failure or severe pneumonia and had not fully recovered their pulmonary function at the time of screening |
HFMSE score < 10 Severe contractures or severe scoliosis Invasive or noninvasive ventilation for > 6 h during a 24-h period at screening Gastric feeding tube Hospitalization for surgery, pulmonary event, or nutritional support within 2 months of screening |
Hospitalization for pulmonary event within the last 2 months Surgery for scoliosis or hip fixation in the 1 year preceding screening or planned within next 18 months Invasive ventilation or tracheostomy |
HFMSE Hammersmith Functional Motor Scale Expanded, MAIC matching-adjusted indirect comparison, SMA spinal muscular atrophy, SMN2 survival motor neuron 2 gene
a81 participants were randomized to the nusinersen group but one infant withdrew from the trial before treatment; infant was not dosed in ENDEAR but was dosed in SHINE
bAlthough all enrolled participants had 2 copies of SMN2, inclusion criteria permitted enrollment of infants with 1 or 2 copies