RAINBOWFISH: Primary efficacy and safety data in risdiplam-treated infants with Presymptomatic spinal muscular atrophy (SMA)


Clinical Trials

Poster Number: S103


Richard Finkel, MD, St. Jude Children’s Research Hospital, Michelle Farrar, PhD, School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Laurent Servais, MD, PhD, University of Oxford, Dmitry Vlodavets, PhD MD, Children Neuromuscular Center, Pirogov Russian National Research Medical University, Moscow, Russia, Edmar Zanoteli, MD, PhD, Hospital de Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Mohammad Al-Muhaizea, King Faisal Specialist Hospital & Research Center-Riyadh, Riyadh, Kingdom of Saudi Arabia, Alexandra PQC Araujo, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, Leslie Nelson, PT, PhD, UT Southwestern Medical Center, Dallas, Texas, USA, Birgit Jaber, MSc, F. Hoffmann-La Roche Ltd, Ksenija Gorni, MD PhD, PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Heidemarie Kletzl, PhD, F. Hoffmann-La Roche Ltd, Laura Palfreeman, Roche Products Ltd, Welwyn Garden City, UK, Eleni Gaki, Roche Products Ltd, Welwyn Garden City, UK, Michael Rabbia, Genentech, Inc., South San Francisco, CA, USA, Dave Summers, Roche Products Ltd, Welwyn Garden City, UK, Paulo Fontoura, MD, PhD, FAAN, F. Hoffmann-La Roche Ltd, Enrico Bertini, MD, Ospedale Pediatrico Bambino Gesu’ IRCCS


In patients with SMA, motor neuron degeneration precedes symptom onset, due to a deficiency of survival of motor neuron (SMN) protein. Risdiplam (EVRYSDI®) is an oral SMN2 pre-mRNA splicing modifier that increases and sustains functional SMN protein levels.

RAINBOWFISH (NCT03779334) is an open-label, single-arm, multicenter study of risdiplam in infants with genetically diagnosed, presymptomatic SMA. The primary endpoint was the proportion of infants with two SMN2 copies and baseline ulnar CMAP amplitude ≥1.5 mV, who were able to sit without support for ≥5 seconds at Month 12 (Item 22, Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition). Secondary endpoints include motor milestone achievement; motor function; nutritional status; growth measures; survival and permanent ventilation; CMAP; development of clinically manifested SMA; and safety monitoring.


To assess the efficacy and safety of risdiplam in infants with presymptomatic SMA.


The median age at first risdiplam dose was 25.0 (range 16−41) days (n=26). The primary endpoint at Month 12 was met with 80% of infants (n=5) able to sit without support for ≥5 seconds. Additionally, 7/8 infants with two SMN2 copies were able to sit without support for ≥30 seconds, including all infants with CMAP amplitude <1.5 mV (n=3). At Month 12, all infants were alive without permanent ventilation and no adverse events (AEs) led to withdrawal or treatment discontinuation. Most AEs were not considered treatment-related and resolved over time. One infant met the criteria for development of clinically manifested SMA. At Month 12, 24/26 infants (92%) were able to sit without support, and many were able to stand (21/26 [81%]) and walk (16/26 [62%]), as assessed by the Hammersmith Infant Neurological Examination, Module 2. Conclusions RAINBOWFISH is ongoing globally to provide additional data on the efficacy and safety of risdiplam in infants with presymptomatic SMA.