Background
Duchenne muscular dystrophy (DMD) is a severe, fatal, irreversible muscle-wasting disease with no cure that causes progressive muscle weakness in early childhood, with loss of ambulation typically occurring by adolescence. Current treatments aim to slow progression and improve quality of life.
Objective
Measurements of PUL 2.0 from the placebo-controlled HOPE-2 study, the gap period, and the ongoing open label HOPE-2-OLE study were used to assess the clinically relevant benefits of deramiocel.
Methods
Changes in PUL 2.0 were analyzed for 13 patients for a total duration of ~5 years across the HOPE-2 study (12 months), Gap Period (~12 months of non-treatment), and HOPE-2-OLE study (36 months).
Additionally, data from a cohort matched external comparator of 30 patients was compared to the results in HOPE-2-OLE using a random effects continuous-time model.
Results
Placebo patients from HOPE-2 who enrolled in HOPE-2-OLE had a 3.8-point decline in the PUL 2.0 in the randomized portion of the trial and further declined an additional 3.7 points during the Gap Period. Deramiocel-treated patients in HOPE-2 who enrolled in HOPE-2-OLE had an initial 1.5-point decline and subsequently experienced a 2.8-point decline during the Gap period when no treatment was administered.
Long-term follow-up in HOPE-2-OLE demonstrated sustained effects, with mean annual decline in PUL 2.0 decreasing from 1.8 points in Year 1 to 1.2 points in Year 2 and 1.1 points in Year 3.
When comparing against the external comparator group, deramiocel-treated patients showed a statistically significant (p=0.019) attenuation of disease progression of 52%. The 36-month difference in the linear change from baseline of favored deramiocel-treated patients by 3.73 points over the external comparator on the total PULv2.0.
Conclusion
The findings from HOPE-2 and HOPE-2-OLE suggest that deramiocel slows disease progression even after treatment interruption and provides long-term benefits in preserving upper limb function.