- Treatment with ezutromid resulted in a statistically significant and meaningful reduction in muscle damage as measured by a 23% decrease in mean developmental myosin in muscle biopsies at 24 weeks compared to baseline (11.37% to 8.76%, 95% CI, -4.33, -0.90). Developmental myosin is a biomarker of muscle damage and is found in repairing fibres.
- A total of 14 of 22 patients showed a decrease in developmental myosin, with five of those showing a greater than 40% reduction.
- Increase in mean utrophin protein intensity levels of 7% in biopsies at 24 weeks compared to baseline (0.370 to 0.396, 95% CI, -0.005, 0.058).
Additional findings from the PhaseOut DMD 24-week interim results:
- All patients achieved plasma levels of ezutromid sufficient to modulate utrophin.
- Pharmacological responses were observed in patients treated with either the F3 or F6 formulations. There were no observed relationships between drug exposure and responses in pharmacology or safety measures at this stage.
- In an additional biopsy measure, average muscle fibre diameter decreased from 42.1µm at baseline to 40.3µm at 24-weeks.
- Changes in muscle pathology can be monitored using magnetic resonance spectroscopy ('MRS') to evaluate the amount of fat in muscles, which increases over time in DMD. The mean fat fraction in the vastus lateralis (thigh) was 14.7% at baseline and 18.5% at 24 weeks (n=37). Longer term dosing of patients is expected to be required to detect changes in MRS parameters, which is the 48-week primary endpoint.
- Functional tests, which naturally decline over time in DMD, were included as exploratory measures. The mean six-minute walk distance was 404m at baseline and 395m at 24 weeks (n=39). Mean North Star Ambulatory Assessment score was 25.0 at baseline and 24.4 at 24 weeks (n=39). The North Star Ambulatory Assessment is a multi-point test of motor function with a maximum score of 34.
- All patients retained ambulation after 24 weeks of treatment.
- Ezutromid has been well tolerated to date.
