Survival in Eteplirsen-Treated vs Duchenne Muscular Dystrophy Natural History Patients: An Indirect Treatment Comparison Using Real-World Data



Poster Number: 183


Joel Iff, PharmD, PhD, Sarepta Therapeutics, Inc., Cambridge, MA, Nicolae Done, PhD, Analysis Group, Inc., Ed Tuttle, Analysis Group, Inc., Boston, MA, Yi Zhong, Analysis Group, Inc., Boston, MA, Fangzhou Wei, Analysis Group, Inc., Boston, MA, Basil Darras, MD, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, Craig McDonald, MD, University of California Davis Health, Eugenio Mercuri, MD, Fondazione Policlinico Universitario A Gemelli, Francesco Muntoni, MD, UCL Institute of Child Health and Great Ormond Street Hospital for Children

Eteplirsen results in attenuation of ambulatory and pulmonary decline in patients with Duchenne muscular dystrophy (DMD) vs natural history (NH) controls. However, impact on survival is unknown.
Using real-world data collected by Sarepta’s patient support program, survival of patients receiving eteplirsen as part of routine care was compared with DMD NH data (2 US-based and 2 European studies). Kaplan-Meier curves were digitized, generating reproduced individual patient data. Survival age was compared between eteplirsen-treated patients and NH controls using unadjusted Kaplan-Meier curves, log-rank tests, Cox models, and parametric specifications. Time from treatment initiation to death was compared in a simulation randomly matching each eteplirsen-treated patient still alive at age of treatment initiation with up to 15 NH controls, adjusted for baseline age and age-treatment interaction.
Among 579 patients, the mean age at eteplirsen initiation was 11.9 years (range 1.0–35.0) and mean exposure was 3.7 years (0.0–8.6). Median age at death was higher for eteplirsen-treated patients vs NH controls (32.8 vs 27.4 years, log-rank P<0.0001), resulting in prolonged median survival of 5.4 years for eteplirsen-treated patients. Hazard of death appeared 66% lower for eteplirsen-treated patients vs NH controls (HR 0.34, 95% CI [0.23, 0.50], P<0.001). Mortality rates were lower for eteplirsen-treated patients vs NH controls across all 5-year segments ranging from 5 to 45 years. Younger initiation and longer treatment exposure were independently associated with longer survival. Results were robust to different combinations of NH controls; data limitations prevented adjusted comparison controlling for prognostic factors. Conclusions These real-world data suggest that eteplirsen may prolong survival in patients with DMD across a wide age range.