MDA 2025: Evrysdi consistent after 5-year SUNFISH follow-up
SMA patients continue to stabilize, see gains in motor function
After five years of treatment with Evrysdi (risdiplam), people with spinal muscular atrophy (SMA) types 2 and 3 continue to see stabilization and improvement in measures of motor function.
That’s according to new long-term data from the Phase 2/3 clinical trial SUNFISH (NCT02908685), sponsored by Roche, which owns Evrysdi’s developer Genentech. The results were presented at the Muscular Dystrophy Association‘s (MDA) annual Clinical & Scientific Conference in a poster titled, “SUNFISH Parts 1 and 2: 5-year efficacy and safety data of risdiplam in Types 2 and 3 spinal muscular atrophy.”
“SUNFISH provides long-term efficacy and safety data of [Evrysdi] in a broad population of children, teenagers and adults with Types 2/3 SMA,” researchers wrote in their abstract.
SMA is caused by mutations that lead to an abnormally low production of the protein SMN. Evrysdi is an oral therapy designed to boost SMN. It’s approved in the U.S. for all types of SMA and was first developed as an oral solution. A tablet formulation was recently approved in the U.S. as well.
SUNFISH tested the effects of Evrysdi in children and young adults, ages 2-25, with SMA type 2 or 3. In the first part, 51 patients were given various doses of Evrysdi or a placebo. Then, based on those findings, a selected dose of Evrysdi was tested against a placebo in 180 patients in the second part.
The results showed that patients given Evrysdi tended to see improvements or stabilized motor function after a year, whereas patients given a placebo tended to see declines.
Measures of motor function
Following the placebo-controlled part of the trial, participants could enter into an extension phase where all were treated with Evrysdi and monitored for long-term outcomes. Data presented in 2023 showed that the stabilization and improvement in motor function seen in the original study were largely maintained for four years.
Measures used in SUNFISH include the Revised Upper Limb Module (RULM), which measures motor function in the arms and hands, along with the Hammersmith Functional Motor Scale-Expanded (HFMSE) and the Motor Function Measure-32 (MFM-32), two more general gauges.
Average RULM scores increased steadily in the first two years after patients started Evrysdi and stayed stable through the remaining follow-up. At five years, the average RULM score was about 2 points better than before patients started Evrysdi.
Laurent Servais, MD, PhD, lead author of the poster, said this means the average patient can do one thing with their arms that they couldn’t do before, or can now do independently two things that they would’ve needed help with before.
Laurent Servais, MD, PhD, is a professor of pediatric neuromuscular diseases at the MDUK Oxford Neuromuscular Centre in the U.K.
“It can be the ability to lift an object; it can be the ability to bring something to your mouth,” Servais, who is a professor of pediatric neuromuscular diseases at the MDUK Oxford Neuromuscular Centre, said in an interview with SMA News Today.
Servais said the change “is not massive, for sure, but it means that [the patients’ functionality is] also on a trend upward … They are actually improving, and that means a lot.”
Not just stabilization, improvements also
HFMSE scores also increased in the first two years after patients started Evrysdi, but have since declined. At five years, the average HFMSE score was about a point worse than the average score before Evrysdi. Meanwhile, MFM-32 scores have been largely stable throughout the trial and by five years of follow-up, the average MFM-32 score was virtually unchanged compared with pre-Evrysdi scores.
Based on these data collectively, Servais said patients starting Evrysdi can likely expect a small boost in physical function soon after starting the drug that will stabilize or decline slightly in the years that follow. He noted that physical function changes over time in everyone, even people who don’t have SMA, and can be affected by many different factors, so very small fluctuations in these scores aren’t especially meaningful.
Other types of care like physical therapy and regular exercise can have a major impact on patients’ experience of treatment, he said.
“I’m always impressed how … the best responders are patients with the strongest commitment, who will exercise, who move,” he said. “There is no drug that works outside standard of care, outside of the mobilization of the patient.”
In addition to standardized measures of motor function, patients and caregivers also completed the SMA Independence Scale-Upper Limb Module (SMAIS-ULM), a measure of how well people with SMA can function independently in day-to-day life. Both patient- and caregiver-rated SMAIS-ULM scores increased up to two years after starting Evrysdi and have remained stable. At five years of follow-up, patient-rated scores were about 1 point better and caregiver-rated scores were about 2 points better than pre-Evrysdi values.
The improvement in SMAIS-ULM “means that our patients not only are stable, but are improving in that it translates into a daily life activity,” Servais said.
Safety data from the five-year follow-up were consistent overall with earlier data. The most common side effects of Ervysdi include skin issues like eczema and digestive issues like diarrhea, said Servais, who noted that these side effects are usually temporary and stopping treatment is always an option.
Note: The SMA News Today team is providing live coverage of the 2025 MDA Clinical & Scientific Conference March 16-19 in Dallas. Go here to see the latest stories from the conference.
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