Comparison of North Star Ambulatory Assessment score change in nmDMD patients receiving ataluren: STRIDE Registry vs phase 3 clinical trial

Topic:

Other

Poster Number: 98

Author(s):

Pannie Trifillis, PTC Therapeutics Inc., South Plainfield, NJ, USA, Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK, Már Tulinius, MD, Department of Pediatrics, Gothenburg University, Queen Silvia Children’s Hospital, Sweden, Filippo Buccella, Parent Project APS, Rome, Italy, Isabelle Desguerre, Hôpital Necker – Enfants Malades, Paris, France, Janbernd Kirschner, MD, Medical Center-University of Freiburg; University Hospital Bonn, Faculty of Medicine, Andres Nascimento-Osorio, MD, Hospital Sant Joan de Déu, Unidad de Patología Neuromuscular, Universidad de Barcelona, Spain, Shelley Johnson, DBA, MBA, PTC Therapeutics Inc., South Plainfield, NJ, USA, Christian Werner, PhD, PTC Therapeutics Germany GmbH, Frankfurt, Germany, Joel Jiang, PhD, PTC Therapeutics Inc., South Plainfield, NJ, USA, James Li, PTC Therapeutics Inc., South Plainfield, NJ, USA, Rich Able, PhD, PTC Therapeutics, Claudio L. Santos, MD, MBA, PTC Therapeutics Inc., South Plainfield, NJ, USA, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion

Background: Strategic Targeting of Registries and International Database of Excellence (STRIDE) Registry (NCT02369731) is an ongoing, multicenter, observational registry providing data on ataluren use in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients in routine clinical practice.

Objective: We investigated whether nmDMD patients receiving ataluren in real-world practice in the STRIDE Registry (NCT02369731) experienced lesser declines in North Star Ambulatory Assessment (NSAA) total, linear and shift scores vs patients receiving ataluren/placebo in a phase 3 clinical trial (Study 020; NCT01826487).

Methods: The NSAA comprises 17 items, scored to document progressive loss of function. STRIDE patients were assessed by first 48-week score change (difference between their first ‘48-week assessment’ [between 40 and 72 weeks] and their first assessment); Study 020 patients were assessed by change over 48 weeks. The proportion of STRIDE patients who lost the ability to perform NSAA items over the first 48 weeks was compared with Study 020 patients in a shift analysis; item failure was recorded by a shift from a score of 2 (able) or 1 (impaired) to 0 (unable).

Results: In Study 020, ataluren-treated patients experienced a lesser mean decline in NSAA total and linear scores vs placebo-allocated patients over 48 weeks (total score [95% confidence interval [CI]: ataluren,?2.7[?3.5,?1.9]; placebo,?3.7[?4.5,?2.8]; linear score [95% CI]: ataluren,?6.3[?8.3,?4.2]; placebo,?8.4[?10.4,?6.4]). STRIDE patients consistently experienced a mean (95% CI) decline in NSAA total and linear scores of ?1.97(?2.90,?1.05) and ?4.54(?6.75,?2.33) respectively, over their first 48-week assessments.
The proportion of patients who lost the ability to perform NSAA items was greater for Study 020 placebo-allocated patients than ataluren-treated STRIDE and Study 020 patients.

Conclusions: These results demonstrate that ataluren delays decline in performance of NSAA items in nmDMD patients vs placebo, indicating that ataluren delays disease progression.