FDA approves risdiplam to treat presymptomatic babies under 2 months with SMA


Data from the RAINBOWFISH study and a large-scale extension, FIREFISH, were the basis for risdiplam’s expanded indication, which now includes babies with SMA under 2 months old.

The FDA has approved an expanded indication for risdiplam (Evrysdi; Genentech) to include the treatment of presymptomatic babies under 2 months old with spinal muscular atrophy (SMA), making it the first approved treatment administered at home for this patient group. Risdiplam is now approved to treat SMA in both children and adults of all ages.1

The decision to expand risdiplam’s indication was based off interim efficacy and safety data from the RAINBOWFISH study (NCT03779334), which showed that, following 12 months of treatment with risdiplam, a majority of presymptomatic babies met key milestones of healthy babies. This included sitting, standing, and walking, in addition to maintaining the ability to swallow.2

"The approval of Evrysdi for presymptomatic babies is particularly important, as early treatment of SMA, before symptoms start to arise, can help babies to achieve motor milestones,” principal investigator Richard Finkel, MD, director, Experimental Neuroscience Program, St. Jude Children’s Research Hospital, said in a statement.1 "With the inclusion of SMA in newborn screening programs, this approval provides the opportunity to start treating at home with Evrysdi soon after the diagnosis is confirmed."

Risdiplam, a survival motor neuron splicing modifier, also had supportive data from the open-label extension FIREFISH study (NCT02913482) in its application. In a cohort of 58 infants aged 1 to 7 months, 91% were alive after 3 years of 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 the Gross Motor Scale of the Bayley Scores of Infant and Toddler Development.3

"The priority review and subsequent approval of Evrysdi for babies under 2 months of age speaks to the urgent ongoing need for additional treatment options for babies with SMA,” Levi Garroway, MD, PhD, chief medical officer, and head, Global Product Development, Genentech, said in a statement.1 “Because of its efficacy in multiple settings, Evrysdi is now available for people with SMA from presymptomatic newborns to older adults. We are proud of this achievement, which has the potential to make a real difference to those living with SMA and their caregivers."

Among the several ongoing trials of risdiplam, FIREFISH is unique in its 2-part design. Part 1 was a dose-escalation study in 21 infants with the primary end point assessing safety and determining the dosing for Part 2. In the single-arm Part 2, 41 infants with type 1 SMA were treated for 2 years, followed by an open-label extension. Original 2-year data from Part 2 were published in April 2021, with expanded results released in August 2021.

The most recent analysis of FIREFISH, announced earlier this month, pooled participants treated with the agent for a minimum of 3 years. At the conclusion of the analysis, 20 infants maintained and 15 gained the ability to sit without support for at least 30 seconds. No infant who gained the ability to sit without support lost this ability after 3 years, and the majority of infants also maintained the ability to feed orally and swallow up to that time point.3

Most infants showed the ability to improve or maintain measures on the Hammersmith Infant Neurological Examination between 24 and 36 months. This included being able to hold their heads upright (36 maintained, 3 gained, and none lost the ability since month 24), pivot while sitting (15 maintained, 11 gained, and none lost the ability), stand with support (6 maintained, 5 gained, and 1 lost the ability), and walk while holding on (1 maintained, 2 gained, and none lost the ability).

Originally published on our sister brand, NeurologyLive.


1. FDA approves Genentech’s Evrysdi (risdiplam) for use in babies under two months with spinal muscular atrophy (SMA). News release. Genentech. May 31, 2022. Accessed May 31, 2022. https://www.biospace.com/article/releases/fda-approves-genentech-s-evrysdi-risdiplam-for-use-in-babies-under-two-months-with-spinal-muscular-atrophy-sma-/?s=85

2. Roche presents new data at World Muscle Society (WMS) 2021 highlighting new advances for people living with rare neuromuscular disorders. News release. Roche. September 24, 2021. Accessed May 31, 2022. https://www.roche.com/media/releases/med-cor-2021-09-24.htm

3. 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 May 31, 2022. https://www.gene.com/media/press-releases/14950/2022-04-28/new-three-year-data-for-genentechs-evrys

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