Slide 1: Long-Term Functional Outcomes and Safety Following Delandistrogene Moxeparvovec Treatment in DMD: EMBARK 2-Year Results
Long-Term Functional Outcomes and Safety Following Delandistrogene Moxeparvovec Treatment in DMD: EMBARK 2-Year Results Jerry R. Mendell,1 Francesco Muntoni,2 Craig M. McDonald,3 Eugenio M. Mercuri,4 Emma Ciafaloni,5 Hirofumi Komaki,6 Carmen Leon- Astudillo,7 Andrés Nascimento,8 Crystal Proud,9 Ulri
Slide 2: Background and objectives
Background and objectives • Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy for DMD with high affinity for skeletal, respiratory, and cardiac muscles1–4 • Delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin1–4 • Approved in the USA and other sel
Slide 3: EMBARK study design
EMBARK study design PART 1: 52 weeks PART 2: 52 weeks Up to 5 years SINGLE IV INFUSION SINGLE IV INFUSION Key inclusion criteria:1 Delandistrogene • Ambulatory males aged ≥4 to <8 years at Placebo moxeparvovec OPEN-LABEL randomization Randomization EXTENSION • Confirmed DMD diagnosis (DMD mutation f
Slide 4: Part 1 external control (EC) cohort
Part 1 external control (EC) cohort In the absence of a placebo arm, due to the crossover study design, 2-year data of EMBARK Part 1-treated patients were compared with an EC cohort of patients with DMD using propensity-score weighting1* EC cohort entry criteria: Patients receiving only Aged ≥4 an
Slide 5: Part 1 demographics and baseline clinical characteristics
Part 1 demographics and baseline clinical characteristics Baseline characteristics were well matched between patients receiving delandistrogene moxeparvovec in EMBARK Part 1 and EC patients after propensity-score weighting* EMBARK Part 1 Standardized mean Characteristic, Delandistrogene EC cohort di
Slide 6: Part 1: Functional outcomes at 2 years
Part 1: Functional outcomes at 2 years At 2 years, Part 1-treated patients demonstrated statistically significant and clinically meaningful functional benefit versus a propensity-score-weighted EC cohort Delandistrogene Favors delandistrogene moxeparvovec moxeparvovec EC cohort LSM change patients,
Slide 7: Functional outcomes at 2 years
Part 1: Functional outcomes at 2 years At 2 years, Part 1-treated patients demonstrated statistically significant and clinically meaningful functional benefit versus a propensity-score-weighted EC cohort NSAA ∆ 2.88 points; P=0.0001 TTR ∆ –2.06 s; P=0.0033 10MWR ∆ –1.36 s; P=0.0028 3.5 3.5 2 NSAA to
Slide 8: Additional functional outcomes at 2 years
Part 1: Additional functional outcomes at 2 years Other secondary endpoints were stable at Year 2 in Part 1-treated patients SV95C* 100MWR Time to ascend 4 steps 2.5 7 85 Mean (SD), meters/second 6 Time to ascend 4 steps Mean (SD), seconds 2.25 Mean (SD), seconds 75 5 1.97 4 100MWR 65 SV95C 2 1.88 6
Slide 9: Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization up to Week 64
Part 1: Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization up to Week 64 Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization were sustained from Week 12 to Week 64 in a subset of patients treated in EMBARK Part 1* Delandistrogene m
Slide 10: Overview of 2-year safety results
Part 1: Overview of 2-year safety results Between Weeks 52 and 104, Baseline to Week 52 Weeks 52–104* 15 (23.8%) patients Overview of AEs, n (%) N=63 N=63 experienced 34 TR-TEAEs Patients with any TEAEs 62 (98.4) 53 (84.1) One patient experienced two TR-SAEs of Patients with any SAEs 14 (22.2) 5 (7.
Slide 11: Timeline of TR-TEAEs following treatment with delandistrogene moxeparvovec
Part 1: Timeline of TR-TEAEs following treatment with delandistrogene moxeparvovec Evidence to date shows that most TR-TEAEs had first onset within the first 90 days of infusion Number of patients with TR-TEAEs, ranked by frequency at 0–2 weeks, n (%)* Vomiting 31 (49.2) 3 (4.8) 0 (0) 0 (0) 0 (0) Na
Slide 12: Post hoc analysis of 8- to 9-year-old patients treated with delandistrogene moxeparvovec in EMBARK
Post hoc analysis of 8- to 9-year-old patients treated with delandistrogene moxeparvovec in EMBARK Part 2
Slide 13: EC cohort selection for comparison with patients treated at 8–9 years of age
EC cohort selection for comparison with patients treated at 8–9 years of age in EMBARK Part 2 One-year follow-up data of patients treated at 8–9 years of age were compared with a well-matched EC cohort1 of patients with DMD EC cohort entry criteria: Patients receiving only Aged ≥5 and <10 years* c
Slide 14: Part 2 demographics and baseline clinical characteristics: Patients treated at 8–9 years of age
Part 2 demographics and baseline clinical characteristics: Patients treated at 8–9 years of age Part 2 baseline characteristics were well matched between 8- to 9-year-old patients receiving delandistrogene moxeparvovec and EC patients after propensity-score weighting* EMBARK Part 2 Standardized mean
Slide 15: One-year follow-up: Functional outcomes of patients treated at 8–9 years of age
One-year follow-up: Functional outcomes of patients treated at 8–9 years of age At 1 year post-delandistrogene moxeparvovec infusion, patients treated at 8–9 years of age demonstrated statistically significant and clinically meaningful functional benefit versus a propensity-score-weighted EC cohort
Slide 16: Conclusions
Conclusions • Two-year results of patients treated at 4–7 years of age and 1-year results of patients treated at 8–9 years of age indicate stabilization or slowing of Healthy children usually reach the disease progression compared with well-matched 34 peak NSAA score of 34 after age 41 EC cohorts, a
Slide 17: EMBARK: Acknowledgements and disclosures
EMBARK: Acknowledgements and disclosures Acknowledgments • The authors would like to thank the patients and their families for their participation in EMBARK, as well as the investigators and trial staff involved in EMBARK • This study was sponsored by Sarepta Therapeutics, Inc., Cambridge, MA, USA a