Givinostat for treating Duchenne muscular dystrophy (DMD)

Duchenne muscular dystrophy (DMD)

• is an X-linked myopathy marked by a significant mutation in the dystrophin gene, resulting in the absence of functional dystrophin protein
• the absence of functional dystrophin results in inflammation and a progressive, irreversible process whereby the afflicted muscles are successively substituted by adipose and connective tissue

Givinostat mechanism of action (1)

• in dystrophin-deficient muscles, histone deacetylases (HDACs) are hyperactivated, leading to chromatin condensation, which suppresses the expression of genes involved in muscle repair and regeneration
  • by inhibiting class I and II HDACs, givinostat relaxes chromatin, allowing the transcription of key myogenic factors such as MyoD and Myogenin, which drive muscle differentiation and repair
  • givinostat also has anti-inflammatory and anti-fibrotic effects by suppressing NF-κB signaling, thereby reducing the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β
  • also by restoring the activity of myogenic regulatory factors (MRFs), givinostat enhances satellite cell activation and differentiation, promoting the formation of functional muscle fibers and delaying DMD progression

• these combined effects improve muscle strength, fiber integrity, and reduce oxidative stress, demonstrating the drug's potential as a multi-targeted therapeutic for DMD

NICE state (2):

• givinostat can be used as an option to treat Duchenne muscular dystrophy in people 6 years and over who are ambulant (able to walk or stand, with or without support) at the start of treatment

The NICE Committee note:

“..Clinical trial evidence shows that givinostat slows down the loss of ability to climb stairs compared with corticosteroids alone. But, there is no evidence yet on whether givinostat helps delay breathing problems because the trial is still ongoing..When taking into account the condition's severity, and its effect on quality and length of life, the cost-effectiveness estimates are within the range that NICE considers an acceptable use of NHS resources. So, givinostat can be used…”

Reference:

1. Anjum AF, Anjum MB, Rehman RU. Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy. Curr Ther Res Clin Exp. 2025 Mar 25;102:100787.
2. NICE (May 2026). Givinostat for treating Duchenne muscular dystrophy in people 6 years and over.