Genentech, part of the Roche Group, shared encouraging two-year data from the ongoing RAINBOWFISH study at the 29th World Muscle Society Congress (October 8-12, 2024). This study evaluated the efficacy and safety of Evrysdi® (risdiplam) in children with spinal muscular atrophy (SMA) who received treatment pre-symptomatically before six weeks of age (n=23). The results showed that most children reached key motor milestones, were able to swallow and feed orally, and exhibited cognitive skills typical of their peers without SMA, with none requiring permanent ventilation.
“In children with SMA, motor neuron degeneration begins before symptoms appear, making early intervention crucial to preserving muscle function,” stated Dr. Laurent Servais, a Professor of Paediatric Neuromuscular Diseases at the MDUK Oxford Neuromuscular Centre. He emphasized the positive impact of Evrysdi, noting that children receiving early treatment have achieved significant milestones—such as sitting, standing, and walking—that would typically be unattainable without intervention.
In a study of 18 children with three or more SMN2 copies, all achieved standing and walking milestones as evaluated by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Hammersmith Infant Neurological Examination, Module 2 (HINE-2). Most reached these milestones within the World Health Organization’s recommended developmental timelines. Among the five children with two SMN2 copies, all could sit independently, and 60% were able to stand and walk after two years of treatment. Furthermore, all participants could swallow and feed orally, with none requiring permanent ventilation—an important contrast to natural history studies indicating that untreated children with Type 1 SMA typically do not survive past age two.
Cognitive assessments also showed promising results: children in the study demonstrated cognitive skills comparable to those of peers without SMA, as measured by the BSID-III Cognitive Scale. This was the first clinical trial of its kind to evaluate cognitive outcomes as an exploratory endpoint using standardized metrics.
Dr. Levi Garraway, Chief Medical Officer at Genentech, remarked, “These two-year findings underscore the potential of Evrysdi for significantly enhancing the lives of children with SMA. Combined with newborn screening programs, Evrysdi represents the only non-invasive treatment for SMA that can be administered within the first hours of life.”
The study monitored children who began Evrysdi treatment before six weeks of age, with a median initiation at 25 days. Researchers examined outcomes based on the number of SMN2 gene copies, noting that fewer copies are typically linked to more severe SMA.
Importantly, there were no deaths or adverse events that led to treatment discontinuation. The most common side effects included teething, gastroenteritis, diarrhea, eczema, and fever, which were generally consistent with those observed in other Evrysdi trials and reflected typical age-related issues rather than treatment-related complications. Most side effects resolved over time.
Genentech is leading the clinical development of Evrysdi in collaboration with the SMA Foundation and PTC Therapeutics.
About Evrysdi® (risdiplam)
Evrysdi is a splicing modifier for the survival motor neuron 2 (SMN2) gene, aimed at treating SMA caused by mutations on chromosome 5q, resulting in a deficiency of SMN protein. Administered daily in liquid form—either orally or via feeding tube—Evrysdi works by enhancing the production of SMN protein in the central nervous system and peripheral tissues, crucial for maintaining healthy motor neurons and essential functions like swallowing, speaking, and breathing.
Recognized for its innovative approach, Evrysdi received PRIME designation from the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in 2017. It was awarded Drug Discovery of the Year by the British Pharmacological Society in 2021 and is approved in over 100 countries, with reviews ongoing in an additional 12. A room-temperature stable tablet formulation is also under regulatory review.
Evrysdi is being evaluated in several global clinical trials, including:
- FIREFISH (NCT02913482): A pivotal study for infants with Type 1 SMA, which met its primary endpoint.
- SUNFISH (NCT02908685): A double-blind trial for ages 2-25 with Types 2 or 3 SMA, which also met its primary endpoint.
- JEWELFISH (NCT03032172): An exploratory trial for those previously treated with other SMA therapies.
- RAINBOWFISH (NCT03779334): A study involving babies diagnosed with SMA before symptom onset, which met its primary endpoint.
- MANATEE (NCT05115110): A study evaluating the safety and efficacy of a combination treatment in children aged 2-10.
- HINALEA 1 (NCT05861986) and HINALEA 2 (NCT05861999): Phase IV studies assessing Evrysdi’s effectiveness in young patients who received previous gene therapy.
About SMA
Spinal Muscular Atrophy (SMA) is a severe, progressive neuromuscular disorder affecting approximately 1 in 10,000 babies and is the leading genetic cause of infant mortality. Caused by mutations in the survival motor neuron 1 (SMN1) gene, SMA leads to insufficient SMN protein, essential for nerve function. Without adequate SMN protein, nerve cells struggle to function, resulting in muscle weakness and loss of essential physical capabilities, including walking, eating, and breathing.
