Evrysdi’s motor benefits sustained for 2 years in SUNFISH study
Some benefits also seen in patients who transitioned to Evrysdi from placebo
People with spinal muscular atrophy (SMA) types 2 and 3 who received Evrysdi (ridisplam) in the SUNFISH clinical trial and its extension part continued to see improvements or stabilizations in motor function after two years, according to published trial data.
Notably, patients who were originally assigned to a placebo experienced some motor function decline over the first year, but there was a trend toward improvement or stabilization in these measures when patients transitioned to the active treatment in the extension part.
The data overall “demonstrate the clinically meaningful benefits of [Evrysdi] and reinforce a positive benefit-risk profile for the treatment of children, teenagers, and adults with later-onset SMA,” researchers wrote.
These data was published in the Journal of Neurology, in a study, “Two‑year eficacy and safety of risdiplam in patients with type 2 or non‑ambulant type 3 spinal muscular atrophy (SMA).”
Evrysdi approved for all SMA patients in US
An approved disease-modifying therapy for SMA, Evrysdi is indicated for all SMA patients in the U.S., regardless of age, and for patients 2 months and older with SMA types 1, 2, or 3 in Europe. Marketed by Roche, it works to boost the body’s production of SMN, the protein that is lacking in SMA patients.
The Roche-sponsored SUNFISH Phase 2/3 trial (NCT02908685) evaluated the safety and efficacy of once-daily Evrysdi in children and young adults with SMA type 2 or 3, ages 2 to 25.
After an initial dose-finding part, which enrolled 51 participants, the trial’s second part compared Evrysdi against a placebo among 180 patients who could sit independently, but were unable to walk. A total of 120 patients were assigned to receive daily Evrysdi for a year, and 60 people received a placebo.
Motor function was assessed with three scales: the 32-item Motor Function Measure (MFM32), the Revised Upper Limb Module (RULM) score, and the Hammersmith Functional Motor Scale Expanded (HFMSE). Higher scores indicate better motor function in these scales.
The main goal was to assess whether MFM32 scores significantly improved among Evrysdi-treated patients compared with those who received a placebo after a year. Of note, an increase of at least three points on the MFM32 scale is considered a clinically meaningful improvement.
Overall, the gains in motor function after 12 months of [Evrysdi] treatment were maintained or improved upon up to month 24 — confirming the benefit of longer-term [Evrysdi] treatment.
Evrysdi superior to placebo at improving motor function
One-year results demonstrated that Evrysdi led to stabilized or improved motor function for most patients, which is in contrast to the natural course of SMA in which motor function is progressively lost.
Evrysdi was determined to be statistically superior to a placebo at improving motor function, with motor gains particularly pronounced in younger patients. Findings from RULM and HFMSE assessments also hinted at improvements in the Evrysdi group.
Following the first year, 176 participants elected to continue in an open-label extension phase, in which all received treatment with Evrysdi.
Among patients originally assigned to Evrysdi in the placebo-controlled part, all achieved either a stabilization (58%) or improvement (32%) in MFM32 scores after two years compared with pre-treatment evaluations (baseline).
While patients who initially received the placebo experienced motor declines in the first year, 59% stabilized and 16% improved after being on Evrysdi for one year in the extension part.
Notably, motor gains seen in the SUNFISH extension were significantly better compared with patients in a placebo arm of a different SMA clinical trial after one and two years. Those in the comparator group showed progressive motor declines, which was consistent with earlier analyses from SUNFISH’s placebo-controlled part.
RULM scores demonstrated progressive improvements with a longer time on treatment. While HFMSE scores showed numerical increases, these improvements were not statistically significant.
Caregivers report improvements in patients’ daily independence after 2 years
Moreover, caregiver reports indicated improvements in daily independence after two years of Evrysdi, which was not improved in the comparator group. Patients 12 and older reported stabilizations in daily independence during this time.
Respiratory function was not improved with Evrysdi.
Evrysdi’s safety profile was similar to previous findings. The most commonly reported side effects included upper respiratory tract infection, stuffy nose, fever, headache, diarrhea, vomiting, and cough. Pneumonia was the most commonly reported serious adverse event.
“Overall, the gains in motor function after 12 months of [Evrysdi] treatment were maintained or improved upon up to month 24 — confirming the benefit of longer-term [Evrysdi] treatment,” the researchers wrote, noting that for patients with advanced disease, “stabilization of motor function is an important goal of treatment.”
A more recent analysis demonstrated that motor function continues to be maintained or improved after three years of treatment.