First Participant Treated in Phase 4 Study of Nusinersen Treatment After Prior Onasemnogene Treatment 

The first participant in the RESPOND (NCT04488133) study has been treated. In this phase 4 open-label study, infants and children with spinal muscular atrophy (SMA) who continue having unmet clinical needs, despite prior treatment with onasemnogene (Zolgensma; Novartis, Basel, Switzerland), will be treated with nusinersen (Spinraza; Biogen, Cambridge, MA). The 2-year RESPOND study will evaluate whether nusinersen and its mechanism of action may benefit individuals who have had insufficient response to onasemnogene. Efficacy will be measured as progress on motor milestones, evaluated with the Hammersmith Infant Neurological Examination Section 2. Neurofilament protein levels will be measured as a marker of neurodegeneration to evaluate disease activity. 

Children treated with onasemnogene who have suboptimal motor function, the need for respiratory support, abnormal swallowing or feeding; or other factors deemed relevant by the investigator are eligible for inclusion in the RESPOND study. Data from a long-term study (NCT04042025) of onasemnogene show 40% had a suboptimal response and have been subsequently treated with nusinersen. 
 
Initial participants in the study group include 40 infants, age 9 months or less sho have 2 copies of survival of motor neuron 2 (SMN2) and received onasemnogene when they were under age 6 months. A second group will include 20 children with varied age. Participants will a receive 12 mg dose of nusinersen after a screening period followed by maintenance doses every 4 months.