Delayed Pulmonary Progression in Golodirsen-Treated Patients With Duchenne Muscular Dystrophy vs Mutation-Matched External Controls


Clinical Trials

Poster Number: M161


Eugenio Maria Mercuri, MD, PhD, Catholic University, Fondazione Policlinico Universitario A Gemelli IRCCS, Joel Iff, PhD, Sarepta Therapeutics, Inc., Edward Tuttle, MBA, Analysis Group, Inc., Yunjuan Liu, PhD, Analysis Group, Inc., Fangzhou Wei, MS, Analysis Group, Inc., Nicolae Done, PhD, Analysis Group, Inc., Laurent Servais, MD, PhD, University of Oxford, Andreea M. Seferian, MD, Assistance Publique Hôpitaux de Paris, Sorbonne Université, Institut de Myologie, Volker Straub, PhD, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Francesco Muntoni, FRCPCH, FMedSci, University College London, National Institute for Health Research Great Ormond Street Hospital

Pulmonary decline in Duchenne muscular dystrophy (DMD) increases the risk of hospitalization, morbidity, and mortality. Golodirsen is FDA approved for the treatment of DMD in boys with mutations amenable to exon 53 and has been shown in Study 4053-101 (NCT02310906) to have functional benefits in a declining population of patients with DMD vs mutation-matched external controls (ECs). This post hoc analysis compared longitudinal trajectories of percent predicted forced vital capacity (FVC%p) and projected time to cough-assist and nighttime ventilation in patients with DMD receiving golodirsen vs mutation-matched ECs.
Golodirsen-treated patients from Study 4053-101 and the open-label extension 4045-302 (NCT03532542) were required to have ≥2 FVC%p assessments at age ≥10 years at baseline. Mutation-matched ECs were from CINRG-DNHS (NCT00468832), PRO-DMD-01 (NCT01753804), and Study 4658-301 (NCT02255552) and at baseline were age ≤12 years. A linear mixed-effects model adjusting for baseline age and FVC%p was used to analyze FVC%p. Time to cough-assist (FVC%p ≤60) and nighttime ventilation (FVC%p ≤50) was predicted using a linear extrapolation of the model-estimated decline in FVC%p (from average FVC%p readings observed).
At baseline, golodirsen-treated patients (n=20) and ECs (n=17) were well-balanced for age and FVC%p; mean (SD) follow-up was 3.6 (1.8) and 2.4 (1.3) years, respectively. Results from the adjusted model indicated an attenuation of 3.8 percentage points in the annual rate of FVC%p decline for golodirsen-treated patients vs mutation-matched ECs (2.9% vs 6.7%; P<0.01). A previously published analysis of eteplirsen vs mutation-matched ECs demonstrated similar rates of FVC%p decline. The estimated delay in time to reach cough-assist and to reach nighttime ventilation for golodirsen-treated patients vs ECs was 5.6 (~14 vs 19) and 7.5 (~16 vs 23) years, respectively. In conclusion, golodirsen treatment was associated with significant attenuation of pulmonary decline based on FVC%p.