Real world experience of risdiplam in newborns with spinal muscular atrophy (SMA): A multicenter, retrospective cohort study


Clinical Management

Poster Number: S98


Natalie Goedeker, DNP, CPNP, Washington University in St. Louis, Abigail Dierker, DPT, Washington University in St. Louis School of Medicine, Marcia Felker, MD, Riley Hospital at IU Healh, Arpita Lakhotia, MD, Norton Children’s, Amanda Rogers, MD, Norton Children’s, Craig Zaidman, MD, Washington University in St. Louis School of Medicine

Prenatal testing and newborn screening can promptly identify at-risk infants for SMA, but treatment may be delayed due to procurement complexities. The FDA expanded risdiplam indication May 2022 to include infants <2 months. Reported here are interim data on newborns prescribed risdiplam following positive newborn screening or prenatal testing, prior to confirmatory genetic results and urgently procured. We performed retrospective chart review at three centers and identified nineteen infants (2 SMN2 copies, n=8; 3 SMN2 copies, n=6; 4 SMN2 copies, n=3; carriers, n=2). Eighteen infants initiated risdiplam at a mean 10 days. One infant was identified as a carrier before treatment initiation. Another infant identified as a carrier discontinued risdiplam after 5 days of treatment. As of 17 August 2023, mean age at last follow-up was 5 months. All were alive and without ventilatory or feeding support. Nine sat independently at a mean 5.8 months and two walked independently at a mean 11 months, with the remainder below expected age for these skills. All but one with sequential follow-up had gross motor progress and stable (n=2) or improved (n=10) CHOP INTEND scores. One infant without SMA symptoms at risdiplam initiation at 11 days had significant decline at 2 months, with areflexia, weakness, hypotonia, and a 25-point CHOP INTEND decrease. One infant had a single overdose 10x intended dosing without related sequelae. No other adverse events were attributed to risdiplam. Fourteen infants received other SMA therapies (onasemnogene abeparvovec, n=12; nusinersen, n=1; both, n=1). Our interim data suggest newborns can be rapidly and safely treated with risdiplam, which may be useful as a bridge, combination therapy, or monotherapy. Risk of rapid procurement and treatment includes possibility of treating false positive patients. Further long-term studies are warranted. Efficacy and safety data from an upcoming data cut will be shared.