Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy

Pharmacol Res. 2020 Sep;159:104999. doi: 10.1016/j.phrs.2020.104999. Epub 2020 Jun 12.


Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD. Extensive preclinical data was collected in various animal models including dystrophin-deficient (mdx) mice to characterise Rimeporide's anti-fibrotic and anti-inflammatory properties and there is evidence that NHE-1 inhibitors could play a significant role in modifying DMD cardiac and also skeletal pathologies, as the NHE-1 isoform is ubiquitous. We report here the first study with Rimeporide in DMD patients. This 4-week treatment, open label phase Ib, multiple oral ascending dose study, enrolled 20 ambulant boys with DMD (6-11 years), with outcomes including safety, pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. Rimeporide was safe and well-tolerated at all doses. PK evaluations showed that Rimeporide was well absorbed orally reaching pharmacological concentrations from the lowest dose, with exposure increasing linearly with dose and with no evidence of accumulation upon repeated dosing. Exploratory PD biomarkers showed positive effect upon a 4-week treatment, supporting its therapeutic potential in patients with DMD, primarily as a cardioprotective treatment, and provide rationale for further efficacy studies.

Keywords: Cardiomyopathy; Duchenne Muscular Dystrophy; NHE-1; Pharmacokinetic; Rimeporide; Safety.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Child
  • Drug Administration Schedule
  • Europe
  • Humans
  • Male
  • Models, Biological
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Dystrophy, Duchenne / diagnosis
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / physiopathology
  • Neuromuscular Agents / administration & dosage*
  • Neuromuscular Agents / adverse effects
  • Neuromuscular Agents / pharmacokinetics
  • Sodium-Hydrogen Exchanger 1 / antagonists & inhibitors*
  • Sodium-Hydrogen Exchanger 1 / metabolism
  • Treatment Outcome


  • Neuromuscular Agents
  • SLC9A1 protein, human
  • Sodium-Hydrogen Exchanger 1