Comparison of timed function test results in nmDMD patients receiving ataluren: STRIDE Registry vs phase 3 clinical trial

Objectives: We investigated whether ataluren-treated nonsense mutation Duchenne muscular dystrophy (nmDMD) patients in real-world practice (STRIDE Registry; NCT02369731) performed similarly in timed function tests (TFTs) vs ataluren-treated patients in a phase 3 clinical trial (Study 020; NCT01826487). TFTs included time to: run/walk 10 metres (m), climb four stairs, descend four stairs and stand from supine; each measuring progressive loss of function.

Methods: STRIDE patients were assessed by their ‘first 48-week change’ (difference between their ‘48-week assessment’ [between 40 and 72 weeks] and first assessment); Study 020 patients were assessed by change over 48 weeks. Patients who lost ambulation had time to perform TFTs imputed as 30 seconds (s).

Results: Ataluren-treated Study 020 patients experienced smaller mean increases in time (s) to perform TFTs vs placebo-allocated patients (run/walk 10m [95% CI]: ataluren, 2.3 [1.3, 3.3], n=109; placebo, 3.5 [2.3, 4.7], n=110; climb four stairs: ataluren, 2.7 [1.6, 3.7], n=105; placebo, 4.5 [3.0, 5.9], n=103; descend four stairs: ataluren, 2.2 [1.1, 3.2], n=106; placebo, 4.0 [2.4, 5.5], n=100; stand from supine: ataluren, 3.8 [2.7, 5.0], n=101; placebo, 3.9 [2.5, 5.3], n=96). STRIDE patients experienced smaller mean increases in time (s) to perform TFTs vs placebo-allocated Study 020 patients (run/walk 10m [95% CI]: 1.3 [0.6, 2.0], n=113; climb four stairs: 0.4 [−0.3, 1.0], n=73; descend four stairs: 0.3 [−0.1, 0.8], n=59; stand from supine: 1.7 [0.6, 2.8], n=93).

Conclusion: In the real-world and clinical trial setting, ataluren delays decline in TFT performance in nmDMD patients vs placebo, indicating that ataluren delays disease progression.