Advancing treatments for rare diseases together

Rimeporide

28Sep

FDA has granted Rare Pediatric Disease Designation to Rimeporide

FDA, Rimeporide, cardiomyopathy

EspeRare is delighted to announce that the United States Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to Rimeporide, an investigational treatment for cardiomyopathy in children with Duchenne Muscular Dystrophy (DMD). Most of the drugs in development for DMD, approved or used off label, essentially address the skeletal muscles in DMD patients and are aiming to prolong ambulation. Despite being the primary cause of premature death, there are unfortunately no approved dystrophin specific targeted cardiac therapies.

Rimeporide is a first in class, potent and selective Sodium-Hydrogen Exchanger type 1 (NHE-1) inhibitor. By inhibiting NHE-1, it is expected that Rimeporide modulates the damaging ion imbalances that are associated with the lack of dystrophin in DMD patients. Rimeporide was originally developed as a treatment for congestive heart failure (CHF). Rimeporide has recently been tested in a Phase Ib clinical trial in DMD boys (Previtali et al, 2020).

Rimeporide is intended to be administered as a daily oral chronic treatment, in all patients with DMD, regardless of their mutation, and as soon as early signs of myocardial fibrosis are detected. Pending funding, it is planned to launch a worldwide phase II/III clinical study.

This designation represents an important milestone for Rimeporide and EspeRare as we are now eligible to receive a priority review voucher at the time of marketing authorisation approval of Rimeporide by the US FDA.

16Mar

EspeRare’s first clinical study is completed

Rimeporide, Duchenne Muscular Dystrophy, DMD, clinical study

The first clinical study of Rimeporide in boys with Duchenne Muscular Dystrophy (DMD), the RIM4DMD study, has been completed. The study examined the safety, tolerability and pharmacokinetic of Rimeporide, in patients aged 6 to 11 years affected by DMD. Effects on serum and imaging biomarkers were also explored. This RIM4DMD study started in March 2016 in 4 clinical centres in Europe: San Raffaele Hospital (Milano, Italy), Armand Trousseau Hospital/ I-motion (Paris, France), Great Ormond Street Hospital (London, UK) and Santa Creu i Sant Pau Hospital (Barcelona, Spain). The enrolment of 20 patients was completed in December 2017.

The patients received Rimeporide orally for 4 weeks. 4 dose levels were tested, in 4 ascending cohorts with 5 patients taking the drug at each dose level. The decision to progress to the next higher dose was made after review of safety and tolerability data for the preceding dose by an independent Safety Monitoring Committee (SMC).

Good tolerability was demonstrated in all dose cohorts, confirming the results obtained previously in adult subjects. Detailed analysis of the study results is ongoing.

EspeRare is engaging discussions with key opinion leaders in neuromuscular diseases and cardiomyopathy in order to design a phase II /III study which should start at the end of 2018/early 2019, depending on funding.

EspeRare would like to thank the patients and their family for their participation, all the clinicians and clinical sites’ staff for all the work done, as well as the patients organisations for their scientific and financial support, e.g. AFM-Téléthon, Altrodomani Onlus association in Italy, Duchenne Parent Project Italy and Duchenne Parent Project Spain.

04Oct

Rimeporide clinical study presented at the World Muscle Society

Rimeporide, Duchenne, Duchenne Muscular Dystrophy, DMD, World Muscle Society, Poster

The last advances of the Rimeporide clinical study have been presented at the 22nd World Muscle Society congress, in St Malo. Numerous scientists and physicians have shown interest for this project.

Enrollment into this phase IB clinical trial should be complemented by the end of the year. Full results should be available during the first quarter of 2018. EspeRare is initiating discussions with  worldwide clinicians in order to design the phase II study which should start during 2018, depending  on funding.

Poster presented at the World Muscle Society congress

 

26Sep

Rimeporide receives Orphan Drug designation from USA health authorities

Rimeporide, orphan drug, USA, orphan drug designation, orphan disease, rare disease, Duchenne, Duchenne Muscular Dystrophy, DMD

The Food and Drug Administration (FDA), the US Department of Health and Human Services, has granted an Orphan Drug Designation (ODD) for Rimeporide for the treatment of Duchenne muscular dystrophy (DMD). See here for more details.

ODD is designed to promote the development of drugs that may provide significant benefit to patients suffering from rare, life-threatening diseases. In particular, this ODD grants Rimeporide a 7-year data exclusivity in the US.

Rimeporide already received ODD in DMD from the European Medicines Agency in 2015. Further to this designation in Europe, EspeRare has been able to conduct a phase Ib clinical trial of Rimeporide on young DMD patients. This clinical trial will be completed by the end of 2017.

12Jul

Rimeporide in Pulmonary Arterial Hypertension? A collaboration with John Hopkins

preclinical research, Rimeporide, John Hopkins, PAH, NHE-1

In parallel of developing Rimeporide for the treatment of Duchenne muscular Dystrophy, EspeRare is now also initiating studying Rimeporide's therapeutic potential in Pulmonary Arterial Hypertension.

Rimeporide is a discontinued heart failure drug, that EspeRare has turned into an innovative first-in-class treatment for patients with Duchenne Muscular Dystrophy (click here to check this clinical development programme). Rimeporide has proven to be well-tolerated in multiple animal models and clinical trials in healthy adults and young boys with Duchenne.

 The mechanism of action of Rimeporide, the inhibition of a protein called NHE-1, holds potential in multiple therapeutic indications and EspeRare is working towards establishing collaborations with world-class partners to explore this potential.

 In particular, EspeRare started a collaboration with Larissa Shimoda, Ph.D. and John Huestch, M.D. at the John Hopkins University School of Medicine in the "Division of Pulmonary and Critical Care Medicine". The aim of this collaboration is to explore the therapeutic potientiel of Rimeporide in Pulmonary Arterial Hypertension, using in vitro and in vivo models. Over the last 10 years, this team has published important research articles on the contribution of NHE-1 in the development of this debilitating disease and the use of NHE-1 inhibitors to prevent it.

Positive results from this study would support the initiation of a Phase II clinical trial to test Rimeporide’s therapeutic potential in patients with Pulmonary Arterial Hypertension.

22Jun

Presentation by Prof. Muntoni of the Rimeporide study in Duchenne boys

Paediatry, European Paediatric Neurology Society, Congress, Prof. Muntoni, Rimeporide, Duchenne, Duchenne Muscular Dystrophy

Prof Muntoni is the Principal Investigator of the multicenter european phase Ib clinical study in Duchenne Muscular Dystrophy boys. He presented Rimeporide in an oral communication at the 12th European Paediatric Neurology Society Congress in Lyon on June 22nd.

 

On this occasion he gave an update on the preclinical and the clinical development of this innovative treatment that addresses in particular the life-threatening cardiac damage in Duchenne Muscular Dystrophy patients.

19Aug

Rimeporide development in Duchenne initiated

Rimeporide, research, Duchenne

EspeRare starts two research collaborations to demonstrate preclinical efficacy of Rimeporide in Duchenne.

Geneva, Switzerland, August 19, 2013 - The foundation announces that it has started two collaborations with the University of Geneva (Switzerland) and the Children National Medical Center in Washington DC (USA) to develop Rimeporide, its lead programme in Duchenne Muscular Dystrophy (DMD). The objective of these collaborations is to assess the therapeutic utility of Rimeporide for Duchenne patients. Rimeporide is a safe and specific Na+/H+ exchanger type 1 (NHE 1) inhibitor previously developed by Merck Serono for cardiac failure.

Rimeporide preclinical efficacy will be tested in DMD mice models. The assessment will be conducted under the leadership of Dr. Kanneboyina Nagaraju specialized in DMD at Prof. Eric Hoffman's research center for genetic medicine, Children National Medical Center, Washington DC.
In parallel, Dr Olivier Dorchies, a recognised DMD preclinical expert at the Pharmaceutical biochemistry lab of Prof. Leonardo Scappozza, University of Geneva, will also investigate the dose / efficacy relationship of Rimeporide in a mice model  and evaluate the efficacy in various cell lines.

Preliminary data from both collaborations are expected by second quarter 2014.

This preclinical work together with the already available data will support further development of this compound in DMD patients. This program has ultimately the potential to address muscle degeneration and cardiomyopathy in a broad segment of DMD children.