Evrysdi Found to Help Previously Treated SMA Patients in Trial

JEWELFISH 2-year data show therapy worked to stabilize motor function

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Graphs and a medicine bottle are used to illustrate clinical trial data.

Treatment with Evrysdi (risdiplam) increased levels of SMN protein and stabilized motor function in a Phase 2 clinical trial that enrolled spinal muscular atrophy (SMA) patients who had previously been on other therapies, two-year data show.

“These important data demonstrate the safety and efficacy of Evrysdi in a broad, real-world population of people previously treated with an SMA-targeting therapy,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, said in a press release.

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In SMA, genetic mutations in the SMN1 gene lead to reduced production of the SMN protein. This protein loss results in the hallmark SMA symptoms  of muscle weakness and decreased gross motor skills.

Evrysdi is an oral medication designed to boost SMN levels by modulating the activity of a related gene called SMN2. It is marketed by Genentech (a subsidiary of Roche), which developed the therapy in collaboration with PTC Therapeutics and the SMA Foundation.

2-year data from JEWELFISH

The ongoing Phase 2 study JEWELFISH (NCT03032172), launched in 2017, enrolled 174 people with SMA who had previously been on a different therapy.

A total of 76 patients had received Spinraza (nusinersen) and 14 had been on Zolgensma (onasemnogene abeparvovec), both of which are now approved to treat SMA. The other participants had been on either RG7800 (13 participants) or olesoxime (71 participants), both of which are experimental therapies no longer in development.

JEWELFISH included patients ranging in age from 6 months to 60 years — 36% of participants were adults — and the trial was open to SMA types 1, 2, and 3. According to Genentech, this is “the broadest and most diverse patient population ever studied in an SMA trial.”

At the start of the study, roughly two-thirds (63%) of the participants had a score of less than 10 on the Hammersmith Functional Motor Scale Expanded (HFMSE), representing severe disease with limited motor function. Most patients (83%) had scoliosis.

In line with previous findings from JEWELFISH, two-year data showed that scores on measures of motor function — including the HFMSE, Motor Function Measure 32 (MFM-32), and Revised Upper Limb Module (RULM) — were stable compared with what would be expected in untreated SMA.

“Those enrolled in JEWELFISH had very severe disease, with over 80% having scoliosis, so maintaining motor function – especially for a progressive disease – can be potentially life-changing,” Garraway said.

Results also showed that Evrysdi led to a substantial increase in SMN protein levels in all patient groups, regardless of prior treatment. The median increase in SMN levels was approximately twofold, Genentech reported.

The safety profile of Evrysdi in this study was largely in line with what has been reported in prior trials. The most common side effects of treatment include fever, diarrhea, and rash.

Most reported safety events in JEWELFISH were attributable to underlying SMA, and notably, the rate of these events decreased by about 50% after the first six months of treatment and were stable through the rest of the study. The study discontinuation rate was low at about 5% per year.

“The consistent safety profile and exploratory efficacy we have seen in the JEWELFISH study, the largest ever conducted in previously treated patients, reinforces Evrysdi as a meaningful treatment option across SMA populations,” said Claudia Chiriboga, MD, a professor at Columbia University Medical Center in New York and investigator on the study.

“The findings add to our confidence when making treatment decisions for previously-treated patients in need,” Chiriboga said.