Comparison of timed function test results in nmDMD patients receiving ataluren: STRIDE Registry vs phase 3 clinical trial
Eugenio Mercuri, Francesco Muntoni, Már Tulinius, Filippo Buccella, Isabelle Desguerre, Janbernd Kirschner, Andrés Nascimento Osorio, Shelley Johnson, Christian Werner, Joel Jiang, James Li, Panayiota Trifillis
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.
Keywords: DMD; STRIDE; timed function tests.
Eugenio Mercuri
Catholic University
Italy
Francesco Muntoni
University College London, Great Ormond Street Institute of Child Health
United Kingdom
Már Tulinius
Gothenburg University, Queen Silvia Children’s Hospital
Sweden
Filippo Buccella
Parent Project APS
Italy
Isabelle Desguerre
Hôpital Necker – Enfants Malades
France
Janbernd Kirschner
Medical Center – University of Freiburg
Germany
Andrés Nascimento Osorio
Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona
Spain
Shelley Johnson
PTC Therapeutics Inc.
Christian Werner
PTC Therapeutics Germany GmbH
Germany
Joel Jiang
PTC Therapeutics Inc.
United States
James Li
PTC Therapeutics Inc.
United States
Panayiota Trifillis
PTC Therapeutics Inc.
United States
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.
Keywords: DMD; STRIDE; timed function tests.
Eugenio Mercuri
Catholic University
Italy
Francesco Muntoni
University College London, Great Ormond Street Institute of Child Health
United Kingdom
Már Tulinius
Gothenburg University, Queen Silvia Children’s Hospital
Sweden
Filippo Buccella
Parent Project APS
Italy
Isabelle Desguerre
Hôpital Necker – Enfants Malades
France
Janbernd Kirschner
Medical Center – University of Freiburg
Germany
Andrés Nascimento Osorio
Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona
Spain
Shelley Johnson
PTC Therapeutics Inc.
Christian Werner
PTC Therapeutics Germany GmbH
Germany
Joel Jiang
PTC Therapeutics Inc.
United States
James Li
PTC Therapeutics Inc.
United States
Panayiota Trifillis
PTC Therapeutics Inc.
United States
