Vamorolone for treating Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a progressive disorder caused by dystrophin deficiency in muscle.

Activation of the proinflammatory nuclear factor-κB (NF-κB) pathway, is seen soon after birth in muscle of patients with DMD.

Vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug that binds to the same target receptors as the corticosteroid class (glucocorticoid receptor, mineralocorticoid receptor), but shows a distinct chemical structure and differences in mechanism of action (1):

• vamorolone shows less positive gene transcriptional activity (transactivation) than corticosteroids but retains inhibition of nuclear factor κB proinflammatory pathways (transrepression)
• vamorolone is a potent antagonist of the mineralocorticoid receptor, whereas most corticosteroids are agonists
• study found that vamorolone, a dissociative steroidal anti-inflammatory, was able to reduce bone morbidities while retaining efficacy

NICE states that (2):

• vamorolone is recommended, within its marketing authorisation, as an option for treating Duchenne muscular dystrophy (DMD) in people 4 years and over

The NICE committee noted "...evidence from a clinical trial shows that vamorolone improves muscle function compared with placebo. But, it is uncertain whether vamorolone is similar at improving muscle function outcomes, and how well it works in the long term, compared with currently available corticosteroids. Compared with prednisone, the evidence suggests that vamorolone is likely to have fewer side effects, although to what extent is uncertain.."

Reference:

1. Guglieri M et al. Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA Neurol. 2022 Oct 1;79(10):1005-1014.
2. NICE (January 2025). Vamorolone for treating Duchenne muscular dystrophy in people 4 years and over