Roche's Elevidys Shows Benefits in DMD

Participants (n=126) received 1.33x10 vector genomes per kilogram body mass (vg/kg) of Elevidys or placebo. In part one, participants were randomised according to age (4-5y or 6-7y) or NSAA total score at screening (≤22 or >22) to receive either Elevidys or placebo, with a follow-up period for 52 weeks. In part two, participants crossed over - meaning, those who were previously treated with placebo in part one received Elevidys and participants who were previously treated with Elevidys received placebo, with a follow-up period for 52 weeks.

The primary endpoint of the trial was change from baseline in NSAA total score at week 52. Secondary endpoints included:

• i.  The quantity of Elevidys micro-dystrophin protein expression at Week 12 as measured by western blot of biopsied muscle tissue
• ii.  Change from baseline to Week 52 in time to rise from floor
• iii. Change from baseline to Week 52 in 10-m walk/run (10MWR)
• iv .Change from baseline to Week 52 in stride velocity 95th centile (as measured by Syde, a wearable device)
• v.  Change from baseline to Week 52 in 100-m walk/run
• vi. Change from baseline to Week 52 in time to ascend four steps

Two years after treatment with Elevidys, statistically significant and clinically meaningful improvements were observed across three key motor function measures of NSAA, TTR and 10MWR, when compared to a pre-specified propensity-weighted untreated external control group. Functional differences between individuals treated with Elevidys and those in the external control group increased between one and two years after dosing. Together, these results demonstrate consistent, sustained benefit in favour of Elevidys.

Detailed results from year two of the EMBARK study will be shared at an upcoming medical meeting and discussed with health authorities. One-year data from part one of the EMBARK study were published in Nature Medicine in October 2024.(see citation).

For individuals treated in part one, two years after treatment, functional motor improvements include:

Functional endpoints (treated in part one)  :   1) NSAA      2) TTR   3)  10MWR   

Measure compared to the external control group (LSM mean difference) :  1)  +2.88 points (improvement), P<0.0001    2) -2.06 seconds (improvement), P<0.0033 3)  -1.36 seconds (improvement), P<0.0028

Individuals who received a placebo in part one crossed over at 52 weeks and were treated with Elevidys in part two. Despite being one year older than those treated in part one, the crossover treated group (n=59) experienced similar changes 52 weeks after treatment, favouring Elevidys compared to the external control. Individuals treated in part one were between the ages of 4 and 7ears and in part two, individuals were between the ages of 5and 9 years.

For individuals treated in part two, one year after treatment, functional motor improvements include:

Functional endpoints (treated in part one)    1) NSAA  2) TTR  3) 10MWR 

Measure compared to the external control group (LSM mean difference)  1) +2.34 points (improvement), P<0.0001    2) -2.70 seconds (improvement), P<0.0001    3) -1.07 seconds (improvement), P=0.0001

Muscle biopsies from a subset of patients taken 64 weeks after dosing in part one showed consistent and sustained expression of micro-dystrophin, as measured by western blot. Muscle pathology on MRI continues to show minimal progression in underlying muscle pathology and remains highly consistent with the functional benefits shown.

“As Duchenne progresses, children will lose the ability to walk, have difficulty breathing, and develop heart problems, all of which severely impact their health and ability to fully participate in life,” said Prof. Francesco Muntoni, Director of Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children, UK. “Encouraging results from year two of the EMBARK trial suggest that with innovative treatments like Elevidys, the period of mobility and independence can potentially be improved, reducing the physical and emotional challenge Duchenne poses for these young boys and their families.”

See citation- Mendell, JR., Muntoni, F., McDonald, CM. et al. AAV gene therapy for Duchenne muscular dystrophy: the EMBARK phase 3 randomized trial. Nat Med 2025, 31, 332 . https://doi.org/ 10.1038/s41591- 024-03304-z