Risdiplam Tablet for Spinal Muscular Atrophy Receives FDA Approval

Today, the FDA approved the first tablet formulation of risdiplam (Evrysdi) for patients with spinal muscular atrophy (SMA) who are at least 2 years of age and weigh more than 44 lbs, according to an announcement from Genentech.¹ The 5 mg risdiplam tablet can be swallowed whole or dispersed in water, providing the same efficacy and safety as the currently available oral solution based on a bioequivalence study that supported the agency’s decision.

The new 5 mg risdiplam tablet is expected to become available in the next few weeks.

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Risdiplam, an SMN2 pre-mRNA splicing modifier, is the only non-invasive disease-modifying therapy for SMA. By increasing and sustaining SMN protein production in both the central nervous system and peripheral tissues, the therapy helps maintain motor neuron health and function. With the new tablet option expected to become available in the next few weeks, the treatment could offer more flexibility for patients. Unlike the liquid formulation, the tablet can be stored at room temperature.

Risdiplam received its original approval in 2020, making it the first therapy approved for at-home oral administration in patients with SMA.² That approval was based on findings from a pair of clinical trials: FIREFISH (NCT02913482) and SUNFISH (NCT02908685).

In the FIREFISH study, 90% of infants treated were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older, and 41% of infants achieved the ability to sit without support for at least 5 seconds. In the SUNFISH study, statistically significant improvement (1.55 point mean difference; P = .0156) in motor function was observed in treated patients at 12 months (1.36 points; 95% CI, 0.61-2.11) compared with placebo (–0.19 points; 95% CI, –1.22-0.84), as measured by a change from baseline in the Motor Function Measure-32 total score.

Genentech, a member of the Roche Group, developed the therapy in collaboration with the SMA Foundation and PTC Therapeutics. In 2017, the FDA granted risdiplam orphan drug designation, and in 2018, it received PRIME designation from the European Medicines Agency (EMA). It has treated over 16,000 patients worldwide and continues to be evaluated in multiple clinical trials.

Risdiplam is currently being evaluated in the phase 4 HINALEA 1 (NCT05861986) and HINALEA 2 (NCT05861999) studies investigating its effectiveness and safety in patients under 2 years of age who have received the Zolgensma gene therapy, either presymptomatically or post-symptomatically. Additionally, participants are being recruited for the phase 2 PUPFISH study (NCT05808764), an open-label study that examines the pharmacokinetics and safety of risdiplam in infants with SMA who are younger than 20 days old at the time of their first dose.

“Evrysdi has robust potential to modify the SMA disease trajectory, and has already been used to treat thousands of patients to date. This approval marks another significant step forward,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in the statement. “The Evrysdi tablet combines established efficacy with convenience, providing an additional flexible option for SMA management.”

References

1. FDA approves Genentech’s Evrysdi tablet as first and only tablet for spinal muscular atrophy (SMA). News release. Genetech. February 12, 2025. https://www.gene.com/media/press-releases/15052/2025-02-12/fda-approves-genentechs-evrysdi-tablet-a

2. AJMC Staff. FDA approves at-home oral treatment for spinal muscular atrophy. AJMC^®. August 7, 2020. Accessed February 12, 2025. https://www.ajmc.com/view/fda-approves-at-home-oral-treatment-for-spinal-muscular-atrophy