NHE-1 blocker KR-33028

NHE-1 (sodium-hydrogen exchanger 1) blocker KR-33028 for the treatment of muscular dystrophies

Stefan Schäfer, Peacock Pharma, Germany

28th March 2015

Peacock Pharma are investigating the use of a selective NHE-1 (Na/H-exchanger-1) blocker, KR-33028, as a potential therapeutic for the treatment of dystrophin-deficient muscular dystrophies. Calcium overload of skeletal and cardiac muscles is a key contributor to the pathophysiology of muscular dystrophies, and overactivation of NHE-1 may contribute to calcium overload. Consequently, inhibiting NHE-1 may reduce calcium overload and improve muscular function in patients with muscular dystrophies. The applicant has generated some encouraging but limited preclinical pilot data with KR-33028 in the mdx mouse model. These data indicate a possible beneficial effect of KR-33028 on intracellular calcium uptake and grip test performance. Nevertheless, this project is at a relatively early stage of development and the preclinical package is not fully complete. Peacock Pharma are planning additional preclinical work and are developing plans for the First In Man (FIM) study in healthy adult volunteers, and a short duration (14 days) pilot phase 2A study in 15 adult Becker muscular dystrophy (BMD) patients. Overall, TACT advise that the applicant recruits a preclinical and regulatory expert advisory committee to address their preclinical work-package status and planning, and to develop an adequate dossier for obtaining scientific advice, guidance and regulatory input from the regulatory authorities. It is advised that such input be obtained prior to moving forward, to make sure that all data generated in any further work contributes to the design and execution of the next steps, and also contributes to a development/regulatory perspective in case of a positive outcome.

12 Apr 2017