#MDA2022 – Evrysdi Safe at 1 Year in Previously Treated Patients
Treatment with Evrysdi (risdiplam) continues to be safe and well tolerated in people with spinal muscular atrophy (SMA) who have previously received other therapies for SMA, according to one-year data from the JEWELFISH clinical trial.
Results also suggest that motor function has been stable in JEWELFISH participants after a year on Evrysdi.
The findings were presented at the Muscular Dystrophy Association (MDA) 2022 Annual Meeting, being held this week in Nashville, Tennessee, in a poster titled “JEWELFISH: Safety, Pharmacodynamic and Exploratory Efficacy Data in Non-naïve Patients with SMA Receiving Treatment wtih Risdiplam.”
Evrysdi is an oral therapy that is widely approved to treat SMA. It works by increasing levels of the SMN protein, whose defect causes the disease.
The Phase 2 clinical trial JEWELFISH (NCT03032172), launched in 2017, is assessing Evrysdi’s safety, tolerability, and pharmacological properties in people with SMA who have previously received other therapies for the disease.
In the trial, 174 patients were treated with Evrysdi. Among them, 76 had previously received Spinraza (nusinersen) and 14 had received Zolgensma (onasemnogene abeparvovec), both of which are approved to treat SMA. Additionally, 13 participants had previously received RG7800, an experimental therapy that was a precursor to Evrysdi, and 71 had received olesoxime, an experimental therapy whose development was terminated following disappointing clinical trial results.
Of note, among patients previously treated with Sprinaza, the most common reason for switching to Evrysdi was difficulties in administering Spinraza, which is given via an injection into the spine.
The data now presented reflect one year of treatment (data cut-off of Jan. 29, 2021). Pharmacological data showed that treatment with Evrysdi more than doubled levels of SMN protein, and this increase was sustained throughout the trial. The increase was similar among patients regardless of their prior therapies.
Also of note, scores on the 32-item Motor Function Measure (MFM32) — a clinician-reported assessment of functional abilities in people with neuromuscular diseases — were stable throughout the year of follow-up.
Safety data have generally been positive. Among all of the patients, about one in five (roughly 20%) experienced an adverse event (side effect) determined by trial investigators to be related to Evrysdi treatment. The most commonly reported adverse events in the trial included upper respiratory infections, fever, nausea, headache, and diarrhea.
There has been only one serious adverse event attributed to Evrysdi — a type of abnormally fast heart rate called supraventricular tachycardia — and this resolved with continual treatment. There have been no on-study deaths, and just eight participants have discontinued, mostly of their own volition.
Overall, the safety profile of Evrysdi in these patients is similar to what has been seen in people who have never been treated with another SMA therapy, according to researchers.
Editor’s note: The SMA News Today team is providing coverage of the 2022 MDA Clinical and Scientific Conference March 13–16.