Clinical Care Effects of Risdiplam’s Expanded Indication in SMA

Richard Finkel, MD, RAINBOWFISH’s principal investigator and the director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital, offered his take on the recent FDA decision for risdiplam (Evrysdi; Genentech).

In late May, the FDA granted an expanded indication approval to Genentech for risdiplam (Evrysdi) to now include the treatment of presymptomatic babies under 2 months old with spinal muscular atrophy (SMA). This decision makes the survival motor neuron splicing modifier 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 on 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 application was also supported by data from the open-label extension FIREFISH study (NCT02913482). 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

To find out more about the implications of this new indication, NeurologyLive® reached out to Richard Finkel, MD, RAINBOWFISH’s principal investigator and the director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital. He shared his perspective on the data and decision in brief.

NeurologyLive®: What clinical care effects might this approval have for patients with SMA and their physicians?

Richard Finkel, MD: This expansion of the label for risdiplam now provides a third option for parents and physicians to consider in treating babies with SMA under 2 months of age. It has a very favorable safety profile and early efficacy results from the RAINBOWFISH study, which led to this expanded label, suggests that it works really well, similar to nusinersen and onasemnogene abeparvovec.

What should the clinical community know about this therapy in this population, specifically?

The ease of administration—a daily oral drug that can be administered at home—will reduce the burden on many families that do not live near a major medical center or SMA clinic. Also, no screening or on-treatment lab are required or recommended, so no blood sticks to these little babies where drawing blood is often a challenge.

How does this earlier treatment window coincide with newborn screening practices? Is screening occurring enough to identify patients who could possibly benefit from risdiplam?

In the US, more than 95% of babies are now screened at birth for SMA. Getting risdiplam for a patient identified by newborn screening should be very easy once the payers adjust their coverage policies to reflect the change in the label. It is the only drug among the 3 that can be administered in the outpatient clinic and home setting. The other 2 drugs also work very well but require hospital-based outpatient care.

Transcript edited for clarity.

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 June 7, 2022.
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 June 7, 2022.
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.