Objective: To reposition rimeporide as an oral disease modifying treatment for patients with
Duchenne Muscular Dystrophy (DMD). Methods: EspeRare is developing rimeporide, a safe, potent, oral and selective NHE-1 inhibitor
for patients with DMD. Today, translational studies are ongoing to generate value
for rimeporide and ensure its subsequent transition into a pivotal Phase II/III study
in patients with DMD. These translational studies are conducted in Golden Retriever
Muscular Dystrophic Dogs (GRMD), mdx mice and patients with DMD. Results: In cardiomyopathic hamster, rimeporide was shown to prevent hypertrophy and necrosis in
the heart and to improve overall survival. In mdx mice, rimeporide improved specific
force, prevented inflammation and fibrosis in skeletal muscles, in the diaphragm and
in the heart in a clinically and statistically significant manner. After showing a
compelling safety and tolerability in healthy adults, rimeporide is now tested in
an open-label, Phase 1b study in young DMD boys to assess its safety, pharmacokinetics
and to explore biomarkers (serum and NMR-I and NMR-S) after a 4-week treatment with
ascending oral dose. The recruitment in the study has been initiated in March 2017.
To date, on the 15 patients who were enrolled, tolerability has been good with no
significant new risks identified. There have been no serious adverse events (SAE),
no pattern of AE and all AE were considered unrelated to rimeporide. Conclusion: Rimeporide in DMD received Orphan Drug Designation from EMA. Rimeporide has the potential
to be a muscle-sparing agent that may alleviate muscle and cardiac damage and inflammation
in patients with DMD. Its unique ability to prevent cardiomyopathy as well as the
decline in muscle function, with no restriction on age and on genetic subtypes, makes
it an important complement to other treatments restoring dystrophin.
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© 2017 Published by Elsevier Inc.