Open-Label Evaluation of Eteplirsen in Male Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping vs Untreated Control: PROMOVI Trial


Clinical Trials

Poster Number: 71


Erica Koenig, Perry Shieh, MD, PhD, Hoda Z. Abdel-Hamid, Anne Connolly, MD, Deborah Steiner, Wenhua Hu, Baoguang Han


1.Sarepta Therapeutics, 2. David Geffen School of Medicine at UCLA, 3. UPMC Children's Hospital of Pittsburgh, 4. Nationwide Children's Hospital, 5. Sarepta Therapeutics, 6. Sarepta Therapeutics, 7. Sarepta Therapeutics

Background: Eteplirsen received accelerated FDA approval for treatment of DMD patients with mutations amenable to exon 51 skipping. We report results from a phase 3 open-label study evaluating eteplirsen in boys with DMD amenable to exon 51 skipping therapy. Methods: Males aged 7 to 16 years inclusive, with confirmed DMD and frame-shift mutations amenable to treatment by exon 51 skipping, received intravenous (IV) eteplirsen 30 mg/kg/wk for 96 wk. An untreated cohort of boys with DMD not amenable to exon 51 skipping was also enrolled. Outcomes included safety, ambulatory function, dystrophin quantification, and pulmonary function. Results: 78/79 patients received eteplirsen and completed 96 weeks of treatment. Recruitment and retention of patients in the untreated group failed as only 13/30 patients completed the study. Safety was assessed in patients who had received up to 96 weeks of treatment. The most frequently reported adverse events (AEs) were headache, vomiting, and cough. The majority of AEs were mild to moderate and considered unrelated to eteplirsen. There were no treatment discontinuations due to an AE. Eteplirsen-treated patients showed a mean increase in dystrophin over baseline by Western blot. Ambulatory assessments, including loss of ambulation, ability to rise, and NSAA over 96 weeks were reported. Pulmonary function as measured by FVC%p was also evaluated. Comparisons to reported natural history suggest slowing of disease progression with eteplirsen treatment. Conclusion: Overall, 96 weeks of once-weekly IV eteplirsen appeared to be well tolerated. Dystrophin production and ambulatory and pulmonary measures suggest a positive treatment effect of eteplirsen as seen in previous studies. Comparison with the untreated cohort was confounded by withdrawals and considered inappropriate because of recently demonstrated differences in disease trajectories of the mismatched genotypes included. Comparisons to well-matched natural history cohorts are underway.