Santhera Pharmaceuticals has announced positive results from the LIONHEART study, confirming vamorolone’s action as a mineralocorticoid receptor antagonist, which the company says sets it apart from other corticosteroids.

The LIONHEART study in 30 healthy adult male subjects demonstrated a statistically significant increase in the urinary sodium/potassium ratio in the vamorolone arm compared to placebo following a fludrocortisone challenge.

This increased ratio in urine provides clinical evidence for vamorolone’s unique mode of action as a mineralocorticoid receptor antagonist (MRA) in humans, combined with its known properties as a dissociative glucocorticoid receptor agonist.

Cardiac complications such as cardiomyopathy are a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). While treatment with corticosteroids (and ACE inhibitors) has demonstrated a delay in the onset of cardiomyopathy, the addition of MRAs including eplerenone to standard of care has also shown an improvement in left ventricular systolic dysfunction.

“Mineralocorticoid receptor antagonists are strongly recommended but late when cardiac function is already reduced and tend to be used in the presence of myocardial fibrosis as detected in magnetic resonance imaging,” explained Professor Karim Wahbi, Cardiologist at the APHP Hospital Cochin, Paris, France. “What is intriguing about this mechanistic study is whether there is a synergistic benefit of the anti-inflammatory and MRA effects of vamorolone on the evolution of cardiac disease in children who started treatment early or if vamorolone could be of benefit to those who are already experiencing cardiac symptoms and wish to remain on a corticosteroid.”

Vamorolone has a mode of action based on binding to the same receptor as glucocorticoids but modifying its downstream activity. Moreover, it is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes that may be responsible for local drug amplification and corticosteroid-associated toxicity in local tissues.

This mechanism has shown the potential to ‘dissociate’ efficacy from steroid safety concerns.

Diana Spencer, Senior Digital Content Editor, DDW