Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698172
Oral Presentations
Neuromuscular Diseases and Varia
Georg Thieme Verlag KG Stuttgart · New York

Eteplirsen Delays Time to Loss of Ambulation in Patients With Duchenne Muscular Dystrophy Compared With Patients Receiving Standard of Care

André Müller-York
1   Sarepta Therapeutics Germany GmbH, Medical Director, Berlin, Germany
,
Joel Iff
2   Sarepta Therapeutics, Inc., HEOR and Market Access, Cambridge, Massachusetts, United States
,
Charles Gerrits
2   Sarepta Therapeutics, Inc., HEOR and Market Access, Cambridge, Massachusetts, United States
,
Gautam Sajeev
3   Analysis Group, Manager, Boston, Massachusetts, United States
,
James Signorovitch
4   Analysis Group, Managing Principal, Boston, Massachusetts, United States
,
Edward Tuttle
5   Analysis Group, Managing Principal, Menlo Park, California, United States
,
Erica Birk
6   Analysis Group, Associate, Menlo Park, California, United States
,
Intekhab Hossain
7   Analysis Group, Analyst, Boston, Massachusetts, United States
,
Zhiwen Yao
8   Analysis Group, Senior Analyst, Boston, Massachusetts, United States
,
Courtney Ng
9   Analysis Group, Senior Analyst, Menlo Park, California, United States
,
Nathalie Goemans
10   Pediatric Neurology Pediatric, University Hospital Leuven, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

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    Research Question: Eteplirsen treatment has been shown to slow ambulatory and pulmonary decline in patients with Duchenne muscular dystrophy (DMD) and mutations amenable to exon 51 skipping vs natural history controls. In this post hoc analysis, we compared time to loss of ambulation (LOA) in DMD patients receiving eteplirsen 30 or 50 mg/kg IV once weekly vs DMD patients receiving standard of care (SoC; eg, glucocorticoids, TREAT NMD guidelines).

    Methods: Data for DMD patients treated with eteplirsen or SoC were analyzed. Time to LOA was defined as the inability to perform the 6-minute walk test (6MWT). Eteplirsen-treated patient data were obtained from 3 clinical studies (Studies 201/202, n = 12; Study 301, n = 71). SoC patient data were obtained from the placebo arm of the DEMAND III trial (n = 60) and from 2 natural history databases (Italian Group DMD registry database, n = 9; Universitaire Ziekenhuizen, Leuven, n = 3). Weibull parametric survival models were used to estimate the association between treatment groups and time to occurrence of LOA, adjusting for baseline age and 6MWT. Adjusted estimates were obtained for the median time to LOA in each group, and for the proportion of patients with LOA in each group after 1, 2, 3, and 4 years.

    Results: The analyses included 83 eteplirsen-treated patients and 72 SoC patients with a median follow-up of 1.13 years. Seven eteplirsen patients and 15 SoC patients lost ambulation. Eteplirsen delayed LOA 2.1 times longer vs patients receiving SoC (95% CI: 1.2–3.6, p = 0.01). This corresponded to a delay in median time to LOA of 3.4 years (6.5 vs. 3.1 years) with eteplirsen vs SoC for the average 9-year-old initiating treatment. After 4 years, the percentage of patients with preserved ambulation was 3 times higher with eteplirsen vs SoC (82% vs 27%).

    Discussion and Conclusion: Based on the most current and comprehensive follow-up data with adjusted comparisons to SoC, eteplirsen was associated with significant, clinically meaningful delays in time to LOA.


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    No conflict of interest has been declared by the author(s).