Disease Digest: Duchenne Muscular Dystrophy

Disease Overview^1,2

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder that causes progressive muscle weakness and wasting^. It affects approximately 1 in 3600 to 9300 male newborns.

Common symptoms of DMD include:

The unmet need in DMD²

Corticosteroids (CSCs), the current standard of care (SoC) for DMD, are associated with several adverse events (AEs) with long-term use. For instance, prednisone and deflazacort are associated with AEs such as:

Weight gain
Stunting of grwoth
Osteoporosis
Mood disturbances
Adrenal insufficiency

Therefore, there remains a clear unmet need for new treatments, which retain the efficacy of CSCs but reduces their AEs, for patients with DMD.

A potential solution: Vamolorone²

Vamolorone is a first-in-class dissociative steroidal anti-inflammatory drug designed to retain the efficacy of CSCs while reducing their associated toxicities.

Diagram comparing the mechanisms of action of prednisolone and vamorolone in the treatment of inflammation, highlighting their effects on NF-kB inhibition and membrane injury repair. — Vamolorone retains transrepression, which inhibits NF-kB-driven inflammation, and reduces transactivation, which limits metabolic AEs. This mechanism of action leads to functional outcomes in DMD management, such as preservation of anti-inflammatory efficacy of steroids and minimisation of long-term-steroid-use toxicities.

Outcomes from a pivotal study in DMD²

A randomised, double-blind, multicentre study evaluated the efficacy and safety of vamolorone vs. placebo and prednisone in boys with DMD who were CSC-naïve.

Vamolorone met its primary endpoint time to stand from supine (TTSTAND), demonstrating improved motor function vs. placebo across both doses.

Meeting its secondary endpoints, vamolorone also demonstrated numerical improvements in the 6-minute walk test (6MWT) and the time to run/walk 10 metre test (TTRW) vs. placebo, consistent with the primary endpoint.

In terms of safety, vamolorone reduced CSC-associated AEs, preserving growth and maintaining comparable BMI and overall tolerability vs. prednisone.

Clinical implications of these results

Vamolorone may provide clinicians an alternative CSC treatment for patients with DMD with anti-inflammatory efficacy
- Flexibility across the 2–6 mg/kg dose range enables individualised dosing based on clinical observations and patient needs
Comparable TEAEs rates across treatment groups suggest vamolorone may be a well-tolerated treatment option for patients with DMD in clinical practice
The preservation of linear growth and stable BMI may help patients with DMD reduce growth-related complications associated with prolonged CSC use.

Key takeaway: Vamolorone may have the potential to provide therapeutic benefit with improved tolerability vs. SoC CSCs for patients with DMD.

References

1. Muscular Dystrophy UK. Duchenne Muscular Dystrophy (DMD). Available at: https://www.musculardystrophyuk.org/conditions/a-z/duchenne-muscular-dystrophy-dmd/. Accessed 2025.
2. Guglieri M, et al. JAMA Neurol. 2022;79(10):1005–1014.

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