#MDA2022 – Motor Benefits of Evrysdi for Children, Adults in SUNFISH Now at 3 Years
Children and young adults with spinal muscular atrophy (SMA) types 2 and 3 continue to report improved or stabilized motor function after three years of treatment with oral Evrysdi (risdiplam) in the SUNFISH clinical trial.
“The positive long-term efficacy and safety results for Evrysdi in this broad SMA population are important for physicians as they consider Evrysdi as a treatment option for their patients,” Laurent Servais, MD, PhD, a trial investigator and a professor at the MDUK Oxford Neuromuscular Centre, said in a press release.
“In treating people with SMA, our aim is to enable or preserve their independence and patients in the SUNFISH study reported continuous improvement or stabilization in the level of help needed for daily living,” Servais added.
John Day, MD, PhD, a neurologist with Stanford University, discussed the new data at the Muscular Dystrophy Association (MDA) Annual Meeting in the oral presentation, “SUNFISH Parts 1 and 2: 3-year Efficacy and Safety of Risdiplam in Types 2 and 3 SMA.”
“We continue to see the benefit [of Evrysdi], and we’re still not seeing any side effects,” Day said.
The two-part Phase 2/3 SUNFISH clinical trial (NCT02908685) is testing Evrysdi in children and young adults with SMA type 2 or 3, enrolled at ages 2 to 25.
SUNFISH is “really the only controlled study [of an SMA treatment] that includes an adult cohort,” Day said.
He noted that the study also included patients with scoliosis or contractures. Overall, it recruited “a much more significantly affected ‘real world’ population” of patients than most trials, Day said.
Its first part enrolled 51 patients to determine the optimal dose for the trial’s placebo-controlled second part, which enrolled 180 people with SMA.
At the start of this second part, all patients could sit independently, but none could walk. Over its first year, 120 patients were given daily treatment with Evrysdi, with the remaining 60 randomized to a placebo. Participants could then enter into an open-label extension where all are being given Evrysdi.
“The treatment and placebo groups were quite well-matched” in terms of demographics and clinical characteristics, Day noted.
Motor function is being assessed via the Motor Function Measure-32 (MFM32) scale, the Revised Upper Limb Module (RULM) score, and the Hammersmith Functional Motor Scale Expanded (HFMSE). On all three measures, higher scores indicate better function.
Prior trial data showed that outcomes on these measures were significantly better in the Evrysdi than the placebo group after the first year. Evrysdi-treated patients generally had slightly better scores on all three measures, suggesting that for most patients, motor function had stabilized or improved. This notably contrasts what would be expected in SMA without treatment, where motor function gradually worsens over time as the disease progresses.
Trial findings at two years of treatment reported these benefits persisting, and the new data show this trend to be generally consistent up to three years of treatment.
For example, about two-thirds of the participants had stable or increasing MFM32 scores at one year, and this proportion was similar at two and three years. At all of these timepoints, about one-third of SUNFISH patients showed increases of three or more points on MFM32 scores.
Results on the RULM and HFMSE were “very comparable” to trends in MFM32 scores, Day said.
Increasing scores on these measures were also seen among patients who participated in the first part of the SUNFISH study.
Notably, this group included patients who could not sit independently, as well as those who could walk, representing an “even broader group of patients” than in the placebo-controlled study, Day said. In this diverse group, “their improvement is both notable and sustained” with up to three years of Evrysdi treatment, he added.
With three years of total follow-up, nine participants have left the SUNFISH study. A variety of reasons were given for their decisions, but none were because of any problems or side effects related to the medication, Day said.
In general, most safety-related events recorded in the study were associated with the underlying disease, rather than a side effect of Evrysdi’s use, according to Day. He noted that there have been no safety issues concerning eye damage, which were observed in animal studies at high doses of Evrysdi.
“We’re not seeing any [adverse events] that would raise concerns about the toxicity of the drug,” Day said.
Also of note, reports of safety issues generally declined over time in the study — and since most reported safety issues were due to SMA, this likely reflects better control of the disease with continued treatment.
“We are pleased that these long-term results further reinforce the safety and efficacy of Evrysdi and it is especially encouraging to see that adverse events decreased over time,” said Levi Garraway, MD, PhD, the chief medical officer and head of global product development at Genentech, a Roche subsidiary that helps market Evrysdi.
SUNFISH, sponsored by Roche, is due to conclude in September 2023.
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