Santhera Reports Positive LIONHEART Study Results for AGAMREE® (vamorolone)

Santhera Pharmaceuticals announced the positive findings from the LIONHEART study, confirming vamorolone’s role as a mineralocorticoid receptor antagonist (MRA). This sets vamorolone apart from other corticosteroids due to its unique mode of action.

The LIONHEART study was an open-label, randomized, placebo- and eplerenone-controlled study, involving 30 healthy adult male participants. The primary endpoint was achieved, showing a statistically significant increase in the urinary sodium/potassium ratio in the vamorolone group compared to placebo (p<0.0001) following a fludrocortisone challenge. This increase in urinary sodium/potassium ratio supports vamorolone’s unique action as a mineralocorticoid receptor antagonist in humans, complementing its known properties as a dissociative glucocorticoid receptor agonist. These results further highlight the pharmacological distinctiveness of vamorolone compared to other corticosteroids.

Cardiac complications, including cardiomyopathy, are significant causes of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). Although corticosteroids (and ACE inhibitors) have been shown to delay cardiomyopathy onset, the addition of MRAs like eplerenone to standard care has improved left ventricular systolic dysfunction, especially when started early.

Prof Karim Wahbi, a cardiologist at APHP Hospital Cochin in Paris, noted, "Mineralocorticoid receptor antagonists are recommended but often used late when cardiac function is compromised and myocardial fibrosis is present." He added that the LIONHEART study raises questions about the potential synergistic benefits of vamorolone’s anti-inflammatory and MRA effects on early cardiac disease progression in children, or its benefits for those already experiencing cardiac symptoms who wish to continue corticosteroid treatment.

Shabir Hasham, Chief Medical Officer of Santhera, stated, "The LIONHEART study is a significant milestone in demonstrating a cardioprotective potential for vamorolone." He emphasized the ongoing collection of long-term data from patients who have been on vamorolone for up to seven years, which will help better understand its impact on cardiac complications in DMD.

AGAMREE, also known as vamorolone, is a novel drug that binds to the same receptor as glucocorticoids but modifies its downstream activity. It is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes, which may amplify local drug effects and contribute to corticosteroid toxicity. This mechanism potentially separates efficacy from the safety concerns associated with steroids, positioning AGAMREE as a dissociative anti-inflammatory drug and a viable alternative to standard corticosteroids for treating children and adolescents with DMD.

In the pivotal VISION-DMD study, AGAMREE met the primary endpoint of Time to Stand (TTSTAND) velocity improvement compared to placebo (p=0.002) after 24 weeks, demonstrating a favorable safety and tolerability profile. Common side effects included cushingoid features, vomiting, weight gain, and irritability, which were generally of mild to moderate severity.

Current data indicate that AGAMREE, unlike corticosteroids, acts as both a mineralocorticoid antagonist and a dissociative glucocorticoid agonist. It does not inhibit growth or negatively impact bone metabolism, as evidenced by normal bone formation and resorption markers. AGAMREE is approved for treating DMD in the United States, European Union, and the United Kingdom.

The LIONHEART study (SNT-I-VAM-026) was designed to evaluate vamorolone’s MRA effect in 30 healthy adult males after fludrocortisone challenge. The primary endpoint was the urine sodium to potassium (Na/K) ratio and its logarithm at various time points. Further analysis is ongoing, with data to be presented at upcoming medical conferences.

Duchenne muscular dystrophy (DMD) is a rare, X-linked disease that almost exclusively affects males, characterized by inflammation, muscle fibrosis, progressive muscle degeneration, and weakness. Major disease milestones include loss of ambulation, self-feeding, and eventual respiratory and cardiac failure, often reducing life expectancy to before the fourth decade. Corticosteroids remain the standard care for DMD treatment.

Santhera Pharmaceuticals is a Swiss company focused on developing and commercializing innovative medicines for rare neuromuscular diseases. The company holds an exclusive license for AGAMREE (vamorolone) from ReveraGen, which is approved for DMD treatment in the U.S., EU, and UK.