EP.82A prospective study of eteplirsen treatment for Duchenne muscular dystrophy in routine clinical practice: study design and methodology

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by mutations in the DMD gene that encode the protein dystrophin. Lack of dystrophin severely compromises muscle fiber strength, flexibility and stability. Consequently, patients with DMD experience diminished quality of life, disability, and premature death, typically resulting from cardiac or respiratory failure. Eteplirsen was approved by the US FDA in September 2016 for the treatment of DMD in patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. This long-term, prospective, observational study (5-year minimum follow-up) was designed to gather data on patients with DMD receiving eteplirsen, as well as on the clinical course of DMD, in routine clinical practice. A minimum of 200 patients with a confirmed DMD diagnosis will be enrolled. The study will initiate in the US, then expand to other countries. Annual interim analyses of all outcomes of interest will be performed. Efficacy assessments will include loss of ambulation, defined as having a North Star Ambulatory Assessment (NSAA) walk score of 0 and the inability to perform the 10-meter walk test; pulmonary function based on % predicted forced vital capacity and height (standing height and ulnar length); neuromuscular function assessments (NSAA, timed function tests, performance of the upper limbs, Brooke Upper Extremity Scale grade, repetitive movement outcomes, and walk pace); activities of daily living; and quality of life as measured by the Pediatric Outcomes Data Collection Instrument. Safety assessments will include monitoring of all adverse events. This presentation will provide specific details regarding study methods, including study design, sample selection, recruitment, and safety and efficacy evaluations. Details regarding the Duchenne Outcomes Research Interchange, a patient- and physician-reported outcomes data warehouse that is planned to launch in 2019, will also be provided.