Risdiplam Significantly Improves SMA Motor Function After 24 Months


Preliminary 12-month data from the JEWELFISH study in previously treated patients showed rapid and sustained increases in survival motor neuron protein levels.

Levi Galloway, MD, PhD

Levi Galloway, MD, PhD

Two-year data from Part 1 of the SUNFISH trial (NCT02908685) and 12-month data from the JEWELFISH (NCT03032172) trial of risdiplam (Roche/Genentech) demonstrated the treatment’s ability to significantly improve motor function after 24 months as well as showing rapid and sustained increases in survival motor neuron (SMN) protein levels in those with spinal muscular atrophy (SMA).1

Results of the 2 studies, presented at this year’s Cure SMA Annual Conference, June 8—12, 2020, also showed no new safety signals, with an overall adverse event (AE) profile consistent with that of treatment-naïve patients.

“These 24-month exploratory data are important as they are consistent with the medically meaningful results we saw after one year in Part 2 of the SUNFISH study, designed to represent a broad, real-world SMA population,” Levi Garraway, MD, PhD, chief medical officer, and head, Global Product Development, Genentech, said in a statement.

SUNFISH, a pivotal phase 3 trial, observed patients aged 2 to 25 years with Type 2 or 3 SMA over a 24-month period. The trial itself contained 231 patients, with Part 1 data including a broad patient population of 51 patients ranging from those unable to sit to those capable of walking, as well as people with scoliosis or joint fractures.

Exploratory efficacy analysis of Part 1 data from SUNFISH focused on motor function using the Motor Function Measure (MFM) scale. In a weighted analysis comparing the data with robust natural history comparator cohort, MFM total change from baseline at 24 months was greater in patients who received risdiplam (3.99-point difference; 95% CI, 2.34—5.65; P <.0001).

In addition to the change in MFM, researchers noted that treatment with risdiplam led to a median 2-fold increase in blood SMN protein levels after 4 weeks, which was sustained for at least 24 months. The results were consistent with part 2 of the trial, which revealed a change from baseline in total MFM-32 score was significantly higher in non-ambulatory patients treated with risdiplam, compared with placebo (1.55-point mean difference; P = .0156).

Pyrexia (55%), cough (35%), vomiting (33%), upper respiratory tract infections (31%), nasopharyngitis (24%), and oropharyngeal pain (22%) were among the most common AEs throughout the study. Pneumonia was the single serious AE observed and was seen in 3 of the 51 patients (5%). There were no treatment-related safety findings that led to withdrawal from the study.

Genentech, PTC Therapeutics, and the SMA Foundation announced in early February that Part 2 of SUNFISH met its primary and key secondary end points in patients with Type 2 or 3 SMA. The first study to include adults with SMA showed that those treated with risdiplam showed an improvement in Revised Upper Limb Module (1.59-point difference; P =.0028).2

Preliminary 12-month data from JEWELFISH, a trial in people with all types of SMA aged 6 months to 60 years previously treated with other SMA therapies, demonstrated a median 2-fold increase in SMN protein versus baseline in 18 of the 174 patients who completed the study.

Among the 174 patients enrolled, 76 were previously treated with nusinersen (Spinraza; Biogen) and 14 with onasemnogene abeparvovec (Zolgensma; Avexis). The remaining 83 patients had been treated with compounds then being developed by Genentech.

Garraway noted in a statement that Roche/Genentech “are also encouraged to see an increase in SMN protein levels across both the SUNFISH Part 1 and JEWELFISH studies. These data reinforce the potential of risdiplam to make a real difference in the lives of the many people living with SMA.”

In JEWELFISH, the most common AEs observed were upper respiratory tract infections (13%), headache (12%), fever (8%), diarrhea (8%), nasopharyngitis (7%) and nausea (7%). Researchers noted that the drug had a consistent safety profile that was observed in previous studies and did not have any withdrawals due to drug-related safety findings.

The regulatory decision for risdiplam was pushed back from May 24, 2020 to August 24, 2020 by the FDA in early April due to additional data review. The delay was a result of Roche submitting additional data from SUNFISH part 2.3

Last year, in a NeurologyLive Peer Exchange segment, experts in neuromuscular disorders, specifically SMA, discussed treatment with risdiplam as an oral therapy and some of the clinical trial data to that point. Watch that discussion below.


1. Genentech announces 2-year risdiplam data from SUNFISH and new data from JEWELFISH in infants, children and adults with spinal muscular atrophy (SMA)[news release]. South San Francisco, CA: Genentech; Published June 12, 2020. Accessed June 15, 2020. biospace.com/article/releases/genentech-announces-2-year-risdiplam-data-from-sunfish-and-new-data-from-jewelfish-in-infants-children-and-adults-with-spinal-muscular-atrophy-sma-

2. Genentech’s Risdiplam Showed Significant Improvement in Motor Function in People Aged 2-25 With Type 2 or 3 Spinal Muscular Atrophy [news release]. South San Francisco, CA: Genentech; Published February 6, 2020. Accessed June 15, 2020. gene.com/media/press-releases/14836/2020-02-06/genentechs-risdiplam-showed-significant-

3. Roche provides regulatory update on risdiplam for the treatment of spinal muscular atrophy (SMA) [news release]. Basel, Switzerland: Roche; Published April 7, 2020. Accessed June 15, 2020. globenewswire.com/news-release/2020/04/07/2013141/0/en/Roche-provides-regulatory-update-on-risdiplam-for-the-treatment-of-spinal-muscular-atrophy-SMA.htm

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