Data Illustrate Efficacy of Risdiplam in SMA and SRP-9001 in DMD


Findings from studies of the neuromuscular treatments were presented by at the 2021 World Muscle Society Virtual Congress, September 20-24.

Levi Garraway, MD, PhD

Levi Garraway, MD, PhD

Positive findings from the RAINBOWFISH study (NCT03779334) in babies with presymptomatic spinal muscular atrophy (SMA) and data pertaining to SRP-9001 (rAAVrh.MHCK7.microdystrophin; Sarepta Therapeutics), an investigational gene therapy for the treatment of Duchenne muscular dystrophy (DMD), were presented at the World Muscle Society Virtual Congress (WMS), September 20-24. 

Data from the ongoing, open-label RAINBOWFISH trial demonstrated the efficacy of risdiplam (Evrysdi; PTC Therapeutics) when treating presymptomatic babies with SMA, as all 5 participants maintained their ability to swallow and able to feed orally following 12 months of treatment. Additionally, after 12 months, 4 out of 5 babies receiving risdiplam were able to stand and walk independently, in accordance with the established windows for health children from the World Health Organization.1

Also presented at WMS 2021 were data from the open-label SRP-9001-101 trial (NCT03375164) evaluating the efficacy of a single dose of SRP-9001 in treating DMD. Four ambulatory children between the ages of 4 and 7 years with DMD were included in the study, which included 3 years of data and concluded that the gene therapy was well-tolerated and demonstrated key functional assessment, as measured by the North Star Ambulatory Assessments (NSAA). When compared with baseline, participants had an increase in motor ability, which was maintained also over the 3-year period. 

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Part 1 of the SRP-9001-102 (NCT03769116) also had data presented at WDS 2021, with the study meeting its primary biological end point of change in microdystrophin protein impression when compared with baseline. Although it did not demonstrate a statistically significant difference, treatment with SRP-9001 did result in an increase in NSAA total score when compared with patients who received placebo at 48 weeks. No new safety signals were identified in the ongoing, randomized, double-blind, and placebo-controlled trial, which has enrolled a total of 41 boys with DMD. 

“These new data for Evrysdi may help extend the potential benefits of this medicine to the youngest SMA patients. Also, the data from SRP-9001 have helped to optimize the design of the upcoming phase 3 trial for DMD,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, Roche, said in a statement.1 “Our goal is to continue to lead the way in developing transformative medicines for neuromuscular diseases. We are grateful for the partnerships that are helping us to develop new therapies for people impacted by these devastating rare diseases.”

Recent Risdiplam Advances 

While both trials have demonstrated efficacy, additional research is needed. Oral risdiplam treatment over a period of 12 months in patients with type 1 SMA resulted in a higher percentage of infants who met motor milestones, survived without need for ventilation, and showed improvements in motor function than the percentage in natural-history cohorts, according to findings from the FIREFISH clinical trial (NCT02913482) announced earlier in 2021. 

Lead author Basil Darras, MD, director, Neuromuscular Center and Spinal Muscular Atrophy Program, Boston’s Children’s Hospital, and colleagues originally published 2-year data from the study in April 2021, which indicated that the treatment had a significant impact on the primary end point. The milestone of being able to sit without support for at least 5 seconds at month 12 was met by 29% (12 of 41) of participants, significantly higher than the performance criteria of 5% from natural-history data (P <.001).2

Development of SRP-9001

In January this year, MRI findings from the open-label gene transfer study in adolescent patients with DMD indicated that SRP-9001 is an effective therapeutic option for patients with DMD.3 Led by Rebecca J. Willcocks, PhD, department of physical therapy, University of Florida, the Systemic Gene Delivery Clinical Trial for DMD showed robust transgene expression on muscle biopsy (74% to 96%) of fibers, but biopsy data reflects a small sample of muscle where muscle quality in large muscle groups can be objectively and noninvasively measured using quantitative MRI (qMRI) and spectroscopy (qMRS), 2 tools used for monitoring disease progression and therapeutic response.

The researchers noted that between qMRI and qMRS data—including muscle fat fraction and bulk MRI transverse relaxation time—could be reduced in children treated with SRP-9001 compared to an age-matched natural history cohort treated with standard of care, as well as a control group of individuals without DMD.

In 2020, the phase 1/2a nonrandomized controlled SRP-9001-101 trial revealed that the treatment was well-tolerated with minimal adverse events in ambulatory men with DMD, without preexisting AAVrh74 antibodies and a stable corticosteroid dose.4 

1. Roche presents new data at World Muscle Society (WMS) 2021 highlighting new advances for people living with rare neuromuscular disorders. News release. Roche. September 24, 2021. Accessed September 30, 2021.
2. Genentech’s Evrysdi continues to improve motor function and survival in babies with type 1 spinal muscular atrophy (SMA). News release. Genentech. April 15, 2021. Accessed September 30, 2021.
3. Wilcocks RJ, Forbes SC, Walter GA, et al. Assessment of rAAVrh.74.MHCK7.micro-dystrophin gene therapy using magnetic resonance imaging in children with Duchenne muscular dystrophy. JAMA Netw Open. 2021;4(1):e2031851. doi:10.1001/jamanetworkopen.2020.31851.
4. Sarepta Therapeutics announces positive safety and efficacy data from the SRP-9001 micro-dystrophin gene therapy trial published in JAMA neurology. News release. Sarepta Therapeutics. June 15, 2020. Accessed June 19, 2020.
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