Sarepta Therapeutics (SRPT) Status Update summary

Study design and methodology

• EMBARK is a multinational, phase 3, randomized, double-blind, placebo-controlled, two-part crossover study in DMD patients aged 4–7 years, with a primary readout at one year and crossover at year two, using external controls for comparison after all patients received treatment.

• Propensity-weighted external control cohorts were used for key endpoints, ensuring well-matched baseline characteristics.

• MRI and functional endpoints (NSAA, time to rise, 10-meter walk/run) were primary measures, with muscle health assessed via fat fraction and T2 signal.

Efficacy and functional outcomes

• Statistically significant improvements were observed in NSAA, time to rise, and 10-meter walk/run at both one and two years post-treatment compared to external controls, with sustained and clinically meaningful benefits indicating disease stabilization and divergence from natural DMD progression.

• At two years, Elevidys-treated patients showed a 2.88-point NSAA benefit, 2.06-second improvement in time to rise, and 1.36-second benefit in 10-meter walk/run, all with p-values <0.0001.

• Functional gains were consistent across age groups, with early treatment leading to better muscle preservation.

• All patients remained ambulatory throughout the two-year study period.

Muscle health and biomarker findings

• MRI data at two years showed minimal progression in muscle fat fraction and inflammation, with levels well below those seen in placebo at one year, supporting the observed functional improvements.

• Delaying treatment resulted in irreversible muscle damage, emphasizing the importance of early intervention.

• Sustained expression of 9001 dystrophin was observed from week 12 to week 64, supporting long-term functional benefits.

• Creatine kinase and other biomarkers continued to show sustained effects, with more data to be released.