RAINBOWFISH: 2-year efficacy and safety data in risdiplam-treated infants with presymptomatic spinal muscular atrophy (SMA)

Topic:

Clinical Trials

Poster Number: O281

Author(s):

Richard S Finkel, MD, St. Jude Children’s Research Hospital, Laurent Servais, MD, PhD, MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre, Oxford, UK, Dmitry Vlodavets, PhD MD, Russian Children Neuromuscular Center, Edmar Zanoteli, PhD, HOSPITAL DAS CLÍNICAS DA FACULDADE DE MEDICINA DA U S P-SP, Mohammad Al-Muhaizea, Department of Neurosciences, King Faisal Specialist Hospital & Research Center-Riyadh, ALEXANDRA PRUFER, PhD, Universidade Federal do Rio de Janeiro, Leslie Nelson, PT, PhD, Department of Physical Therapy, 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 and Rare Disease, F. Hoffmann-La Roche Ltd, Basel, Switzerland, Heidemarie Kletzl, PhD, Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, Laura Palfreeman, Roche Products Ltd, Eleni Gaki, Roche Products Ltd, Michael Rabbia, Genentech, Inc., Dave Summers, Roche Products Ltd, Paulo Fontoura, PDMA Neuroscience and Rare Disease, F. Hoffmann-La Roche Ltd, Michelle A Farrar, PhD, Sydney Children’s Hospital Network and UNSW Medicine, UNSW Sydney, Enrico Bertini, MD, Ospedale Pediatrico Bambino Gesu’ IRCCS

Background

In patients with SMA, motor neuron degeneration begins before the onset of symptoms. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral survival of motor neuron 2 (SMN2) pre‑mRNA splicing modifier that increases and sustains levels of functional SMN protein.

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–6 weeks old at first dose.

The study enrolled 26 infants with two (n=8), three (n=13) and ≥4 (n=5) SMN2 copies. The median age at first risdiplam dose was 25 (range 16−41) days. At Month 12, the primary endpoint was met, with 4/5 (80%) infants with two SMN2 copies and baseline ulnar compound muscle action potential amplitude ≥1.5 mV, sitting without support for ≥5 seconds (assessed by the Bayley Scales of Infant and Toddler Development, third edition [BSID-III]).

Objectives

This analysis assesses the efficacy and safety of risdiplam in infants with presymptomatic SMA after 2 years of treatment.

Results

Twenty-three infants completed 2 years of treatment with risdiplam (data cut-off: March 27, 2024). After 2 years, the majority of infants were able to sit and walk without support (assessed by the BSID-III and Hammersmith Infant Neurological Examination, Module 2), and most achieved age-appropriate motor milestones within the WHO windows of typical development.

For infants who completed 2 years of treatment, mean scaled scores from the BSID-III cognitive scale were consistent with skills typical of normal child development. All infants maintained feeding and swallowing abilities, and none required respiratory or nutritional support. Most infants (92%) did not require hospitalization over 2 years of risdiplam treatment.

No treatment-related adverse events led to withdrawal or treatment discontinuation.

Conclusions

RAINBOWFISH is ongoing globally to provide additional safety and efficacy data of risdiplam in infants with presymptomatic SMA.