Risdiplam Gets Priority Review for Presymptomatic SMA in Babies Under 2 Months


The submission to the FDA is supported by interim data from the RAINBOWFISH trial (NCT03779334), as all 5 babies treated with risdiplam maintained the ability to swallow and feed exclusively orally after 12 months.

Levi Garraway, MD, PhD

Levi Garraway, MD, PhD

A supplemental new drug application (sNDA) for risdiplam (Evrysdi; PTC Therapeutics) has been granted priority review by the FDA for treatment of presymptomatic babies under 2 months of age with spinal muscular atrophy (SMA). The treatment is currently used to treat SMA in adults and children 2 months of age and older, and if approved, the sNDA will make risdiplam the first medicine administered at home for presymptomatic babies with SMA.

The submission incorporates interim data from the RAINBOWFISH study (NCT03779334), which suggest that following 12 months of treatment with risdiplam, a majority of presymptomatic babies met key milestones of healthy babies, including sitting, standing, and walking, in addition to maintaining the ability to swallow. Data were presented at the World Muscle Society (WMS) Virtual Congress 2021, September 20-24. 

“Treating very young babies with Evrysdi before SMA symptoms arise may help them to achieve milestones such as standing and walking within timeframes typical of healthy infants,” Levi Garraway, MD, PhD, chief medical officer, and head of Global Product Development, Genentech, said in a statement.1 “Extending treatment access for the youngest members of the SMA community is crucial and we look forward to working with the FDA on this application.”

The RAINBOWFISH study included 5 babies, all of whom maintained the ability to swallow and feed exclusively orally after 12 months of treatment. Additionally, after 12 months, 4 out of 5 babies (80%) receiving risdiplam were able to stand and walk independently, in accordance with the established windows for health children from the World Health Organization.2

There were no treatment-related serious adverse events reported during the interim safety analysis treatment, but 4 treatment-related adverse events were reported, which were all resolved or in the process of resolving during ongoing treatment. The most common adverse events (AEs) reported were nasal congestion (33%), cough (25%), teething (25%), vomiting (25%), eczema (17%), abdominal pain (17%), diarrhea (17%), gastroenteritis (17%), papule (17%), and pyrexia (17%). Recruitment for RAINBOWFISH is ongoing, and AEs were noted as being reflective of age rather than underlying SMA. 

READ MORE: Application Accepted for Oral Edaravone in Amyotrophic Lateral Sclerosis

Future data from the RAINBOWFISH study are anticipated to be presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in March 2022. Risdiplam is also being evaluated in 4 other clinical trials in people with SMA, including FIREFISH (NCT02913482) in infants with type 1 SMA, with previously reported findings indicating oral risdiplam treatment resulted in a higher percentage of infants who met motor milestones, survived without need for ventilation, and showed improvements in motor function than the percentage in natural-history cohorts. 

Also ongoing is the SUNFISH trial (NCT02908685), evaluating the treatment in patients between the age of 2 and 25 years with Types 2 or 3 SMA, which met its primary end point of sustained or improved motor function after 24 months of treatment. The open-label exploratory JEWELFISH trial (NCT0303172) will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with SMA between the age of 6 months and 60 years who received other investigational or approved therapies for SMA at least 90 days prior to receiving risdiplam, having just completed enrollment (n = 174). 

The final study is MANATEE (NCT05115110), a global phase 2/3 clinical study that will evaluate GYM329 (RO7204239) in combination with risdiplam for the treatment of SMA in patients between the ages of 2 and 10 years. GYM329, an anti-myostatin molecule targeting muscle growth, was granted orphan drug designation in December 2021, with the study beginning recruitment in the first quarter of 2022.

1. Genentech’s Evrysdi (risdiplam) granted FDA priority review for treatment of presymptomatic babies under 2 months of age with spinal muscular atrophy (SMA). News release. Genentech. January 25, 2022. Accessed January 25, 2022. https://www.biospace.com/article/releases/genentech-s-evrysdi-risdiplam-granted-fda-priority-review-for-treatment-of-pre-symptomatic-babies-under-2-months-of-age-with-spinal-muscular-atrophy-sma-/
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 September 30, 2021. https://www.roche.com/media/releases/med-cor-2021-09-24.htm
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