Six-Year Long-Term Safety and Efficacy of Golodirsen in Patients With DMD vs Mutation-Matched External Controls


Clinical Trials

Poster Number: M162


Eugenio Maria Mercuri, MD, PhD, Catholic University, Fondazione Policlinico Universitario A Gemelli IRCCS, Francesco Muntoni, FRCPCH, FMedSci, University College London, National Institute for Health Research Great Ormond Street Hospital, 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, Laurent Servais, MD, PhD, University of Oxford, Ewa Wilk-Durkiewicz, Sarepta Therapeutics, Inc., Xiao Ni, PhD, Sarepta Therapeutics, Inc., Ping Gao, PhD, Sarepta Therapeutics, Inc., Menghan Hu, PhD, Sarepta Therapeutics, Inc., Joel Iff, PhD, Sarepta Therapeutics, Inc., Lorna Hill, Sarepta Therapeutics, Ihor Sehinovych, PharmD, Sarepta Therapeutics, Larry Orogun, MD, MSc, Sarepta Therapeutics

Golodirsen is FDA approved for the treatment of Duchenne muscular dystrophy (DMD) in patients with exon 53 skip-amenable mutations. Results from Study 4053-101 (NCT02310906) and the open-label extension (OLE) 4045-302 (NCT03532542) evaluating the safety and efficacy of golodirsen treatment up to ~6 years in patients with progressive disease deterioration are described. Post hoc analyses comparing ambulatory and pulmonary function of golodirsen-treated patients with matched (including age, mutation, steroid use) external controls (ECs) were performed. Twenty-five patients received treatment at mean age 8.8 years; 18/25 (72%) completed the OLE up to 6.49 years. Overall, golodirsen was well tolerated: treatment-emergent adverse events were generally mild, nonserious, and unrelated to treatment; there were no treatment-related discontinuations, kidney abnormalities, or port-related infections in the OLE. At year 3, loss of ambulation (LOA) occurred in 4/25 (16%) of golodirsen-treated patients compared with 12/54 (22.2%) age- and mutation-matched ECs, representing a 91.1% risk reduction (HR 0.089; P=0.0224). Over 6 years, 15 golodirsen-treated patients experienced LOA (10.7–19.5 years), with 7 patients still ambulant at OLE completion (12.4–20.3 years). Compared with age- and mutation-matched ECs (n=16), golodirsen-treated patients experienced a median delay in time to LOA of ~2.4 years, representing a 47.4% risk reduction (HR 0.526; P=0.149). A separate post hoc analysis suggested that golodirsen-treated patients (≥10 years) experienced a statistically significant and clinically meaningful attenuation in the annual rate of percent predicted forced vital capacity decline compared with mutation-matched ECs (2.9% vs 6.67%; P<0.01). Overall, golodirsen treatment up to ~6 years demonstrates a favorable, consistent safety profile and supports its long-term efficacy vs mutation-matched ECs. This is the longest follow-up of safety and functional benefit of golodirsen in a declining DMD population.