RAINBOWFISH: 3-year efficacy and safety data of risdiplam in children with presymptomatic spinal muscular atrophy (SMA)

Topic:

Clinical Trials

Poster Number: 121 S

Author(s):

Richard S Finkel, MD, Center for Experimental Neurotherapeutics, St Jude Children’s Research Hospital, Memphis, TN, USA, Maria Mazurkiewicz-Bełdzińska, MD, Department of Developmental Neurology, Medical University of Gdańsk, Gdańsk, Poland, Laurent Servais, MD PhD, University of Oxford, Michelle Farrar, MD, UNSW Sydney, Dmitry Vlodavets, MD, PhD, Pirogov Russian National Research Medical University, Moscow, Russia, Edmar Zanoteli, MD, Department of Neurology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil, Mohammad Al-Muhaizea, MD, Neuroscience Centre of Excellence, King Faisal Specialist Hospital & Research Center-Riyadh, Riyadh, Alexandra PQC Araújo, MD, Pediatrics Department, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Br, Leslie Nelson, MPT, PhD, University of Texas Southwestern Medical Center, Manni Kuthiala, MSc, Pharma Development, Safety, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Ksenija Gorni, MD, PhD, PDMA Neuroscience, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Heidemarie Kletzl, PhD, Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland, Francis Warren, PhD, Roche Products Ltd, Welwyn Garden City, UK, Eleni Gaki, MD, Roche Products Ltd, Welwyn Garden City, UK, Dave Summers, MSc, Roche Products Ltd, Welwyn Garden City, UK, Marianna Manfrini, MD, PhD, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Enrico Bertini, MD, Bambino Gesù Children’s Research Hospital IRCCS, Rome, Italy

Background
Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier approved for the treatment of SMA.

RAINBOWFISH (NCT03779334) is a global, open-label, single-arm, multicenter, Phase 2 study assessing the efficacy, safety, pharmacokinetics, and pharmacodynamics of risdiplam in infants with genetically diagnosed and presymptomatic SMA from birth to 6 weeks of age (at first dose), regardless of SMN2 copy number or baseline compound action potential (CMAP).

RAINBOWFISH enrolled 26 infants: eight infants had two SMN2 copies, 13 infants had three SMN2 copies, and five infants had ≥4 SMN2 copies. The primary efficacy (PE) population (n=5) had two SMN2 copies and baseline CMAP amplitudes ≥1.5 mV. Drug dosage was adjusted to achieve a target exposure of approximately 2,000 ng∙hr/mL.

The primary endpoint was met after 12 months of risdiplam treatment, with 4/5 (80%) infants in the PE population able to sit without support for ≥5 seconds (Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, third edition).

Objectives
This analysis assesses the efficacy and safety of risdiplam in children with presymptomatic SMA after 3 years of treatment.

Results
Twenty-three children completed 3 years of treatment with risdiplam (data cutoff: February 10, 2025). The vast majority of children who reached Year 3 (21/23, 91%) were able to sit, stand, and walk without support, and once achieved, no children lost any abilities. All children who completed 3 years of risdiplam treatment were able to swallow and 96% of children were fed exclusively orally. Cognitive function and speech development were similar to that of typically developing children without SMA in the same age range.

There were no treatment-related serious adverse events reported up to Year 3. No child required respiratory support outside of an illness and the majority of children (21/26) did not require any hospitalizations up to Year 3. There were no new withdrawals from treatment between Years 2 and 3.

Conclusion
The majority of children treated with risdiplam before the onset of SMA symptoms, maintained motor milestones and bulbar function and showed cognitive skills similar to children without SMA after 3 years of treatment.