RAINBOWFISH Results Highlight Risdiplam as Effective Treatment for Presymptomatic SMA


After 1 year of treatment with risdiplam, 81% of the 26-infant cohort were able to sit independently for 30 seconds, a milestone not typically reached in SMA.

Richard Finkel, MD, director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital

Richard Finkel, MD

At the 28th World Muscle Society Congress, held October 3-7, in Charleston, South Carolina, Genentech presented new positive data from the phase 3 RAINBOWFISH trial (NCT03779334) assessing risdiplam (Evrysdi) in infants with presymptomatic spinal muscular atrophy (SMA). All told, the agent met its primary end point, with most treated patients achieving motor milestones not typical for the natural history of SMA.1

RAINBOWFISH is an ongoing, open-label trial comprised of 26 babies with genetically diagnosed SMA who received risdiplam prior to the onset of symptoms. In the primary efficacy population (n = 5), which include babies with 2 SMN2 copies and a compound muscle action potential (CMAP) amplitude of at least 1.5 mV at baseline, findings showed that 80% of patients were able to sit without support for at least 5 seconds after 1 year of risdiplam treatment. These motor milestones were assessed using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III).

At the 1-year time point, 81% of the 26-patient cohort could sit independently for 30 seconds, including all infants with low CMAP amplitude at baseline (<1.5 mV), and the majority were standing and walking. In an exploratory analysis using BSID-III, results indicated that treated children continued to have cognitive skills typical of normal child development. According to Genentech, RAINBOWFISH is the first trial to assess cognition with a standardized scale as an exploratory end point.

"These data reinforce the value of beginning treatment for SMA before symptoms appear, with the goal of preserving motor neurons while they are still abundant," principal investigator Richard Finkel, MD, director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital, said in a statement.1 "Coupled with widespread newborn screening programs, early treatment could counteract the effects of the disease to give babies with pre-symptomatic SMA the best possible start in life."

In terms of safety, the majority of adverse events (AE)s were not considered treatment-related, but rather reflective of the age of the babies. Of note, there were no deaths or AEs leading to withdrawal or treatment discontinuation. The most common AEs were teething, COVID-19, pyrexia, gastroenteritis, eczema, and constipation, which were generally consistent with previous studies of risdiplam.

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Risdiplam, an SMN2-splicing modifier, had its indication expanded in May 2022 to include the treatment of presymptomatic babies under 2 months old with SMA using interim efficacy and safety data from RAINBOWFISH. In addition to RAINBOWFISH, the approval was supported by data from the open-label extension FIREFISH study (NCT02913482), a 2-part clinical trial of infants with SMA Type 1. In FIREFISH, 91% of the 58-cohort of infants were alive after treatment with risdiplam. Among the 48 infants who had an available motor assessment, 32 infants maintained and 4 gained the ability to sit without support for at least 5 seconds since month 24, as assessed by BSID-III.2

"Evrysdi is the only non-invasive SMA treatment and can be used within hours of birth, potentially allowing these babies to sit, stand and walk, similar to healthy individuals,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, said in a statement.1 "Evrysdi has now demonstrated its safety and efficacy in babies, children and adults, and these compelling data continue to reinforce our confidence in this treatment."

Risdiplam is currently being evaluated in an extensive clinical trial program that includes a phase 2/3 study assessing its effects in combination with GMY329, an anti-myostatin molecule targeting muscle growth. Otherwise known as MANATEE (NCT05115110), the global trial is currently recruiting and is expected to include patients with SMA aged 2-10 years old.

1. Majority of newborn babies with spinal muscular atrophy (SMA) treated with Genentech’s Evrysdi able to sit independently after 1 year of treatment. News release. Genentech. October 4, 2023. Accessed October 5, 2023. https://www.businesswire.com/news/home/20231003446568/en/Majority-of-Newborn-Babies-With-Spinal-Muscular-Atrophy-SMA-Treated-With-Genentech%E2%80%99s-Evrysdi-Able-to-Sit-Independently-After-1-Year-of-Treatment
2. New three-year data for Genentech’s Evrysdi (risdiplam) show long-term improvements in survival and motor milestones in babies with type 1 spinal muscular atrophy. News release. Genentech. April 28, 2022. Accessed October 5, 2023. https://www.gene.com/media/press-releases/14950/2022-04-28/new-three-year-data-for-genentechs-evrys
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