An interim analysis of data generated in the JEWELFISH trial of risdiplam has been published in the scientific journal, Neurology and Therapy.
The aim of this intermediate report was to present early data on the safety of risdiplam in a range of people with SMA, who had previously been enrolled in an SMA clinical trial or been treated with an approved SMA drug. Also assessed were the drug pharmacodynamics, which provides information on what the drug does to the body (e.g., whether SMN protein levels are affected).
A total of 174 participants were enrolled in the study, aged between 1 and 60 years (median of 14 years) and with a diagnosis of SMA Type 1, 2 or 3. Most participants (78%) possess three copies of the SMN2 gene. All participants included in the preliminary analysis had received daily oral doses of risdiplam for at least 1 year.
Those included in the trial belonged to one of four groups; they had either participated in the MOONFISH trial of risdiplam (13 people, 3 of which had received placebo), or had received olesoxime (71 people), nusinersen (76 people) or onasemnogene abeparvovec (14 people).
Similar to previous trial results, no safety issues with risdiplam were identified after 12 months of treatment, and there were no drug-related safety issues causing participant withdrawal from the trial.
Increased SMN protein levels in blood were identified in the treatment population, similar to previous reports from the FIREFISH and SUNFISH trials of risdiplam. After 4 weeks of treatment, risdiplam resulted in a median two-fold increase in SMN levels compared to baseline (i.e., the value recorded at the start of the study), which was largely sustained over the year treatment period.
As expected, the baseline SMN levels tended to be higher in participants with SMA Type 2 compared to SMA Type 1, and in those with more copies of SMN2. There was also a trend indicating that participants with more SMN2 copies, produced more SMN protein upon treatment.
No clear differences in SMN protein levels at baseline or after one year of risdiplam treatment were identified between participants in the four different pre-treatment groups.
JEWELFISH is still ongoing and final data from the trial will be reported in due course when participants have received risdiplam for 24 months.