Givinostat (Italfarmaco) OKd for Duchenne Patients in Scotland

 The Scottish Medicines Consortium (SMC) has accepted givinostat (Duvyzat) for restricted use in NHS Scotland for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 6 years or older.  

The recommendation covers patients who are still able to walk when therapy begins, even if they later lose ambulation during treatment.

DMD is a rare, severe genetic condition affecting approximately 2500 individuals in the UK. An estimated 80-100 children in Scotland are living with the disorder.

The X-linked recessive condition stems from mutations in the gene encoding dystrophin, a protein essential for muscle cell strength and stability. Children typically experience declining muscle strength from as early as 2 years old, often needing wheelchairs by age 11-12 years and ventilatory assistance by their late teens.

Mechanism of Action and Dosing

Givinostat is a histone deacetylase (HDAC) inhibitor, though the exact way it benefits patients with DMD is not fully understood. In DMD, loss of dystrophin destabilises muscle fibres, leading to chronic inflammation, fibrosis, and adipogenesis. HDAC activity is abnormally high in these cells, which drives changes that suppress muscle regeneration pathways. 

Givinostat helps muscle cells repair and regenerate by correcting this abnormal activity. It reduces inflammation, limits fibrosis and fatty infiltration, and supports the natural repair processes of muscle tissue.

The recommended starting dose varies based on body weight, ranging from 22.2 mg to 53.2 mg administered orally twice daily.

Clinical Evidence

The SMC advice relied on the phase 3 EPIDYS study, which enrolled ambulant male patients aged 6 years or older with genetically confirmed DMD who could complete functional assessments. Participants received either givinostat or placebo, both combined with corticosteroid therapy, for 18 months.

The primary endpoint measured changes in four-stair climb time, a functional assessment of muscle performance. Treatment with givinostat demonstrated a meaningful 14% reduction in deterioration compared with placebo.

Common treatment-related adverse events included decreased platelet count or thrombocytopenia, increased blood triglyceride levels, and gastrointestinal symptoms such as diarrhoea and abdominal pain. Monitoring of triglyceride levels, blood counts, platelets, and electrocardiograms is recommended, with dose adjustments managing most side effects.

Clinical Impact and Implementation

The SMC recognised givinostat as addressing a significant unmet need in DMD, where no curative therapies exist. Current management relies on physiotherapy, corticosteroids, and supportive care.

Clinical experts highlighted givinostat’s novel mechanism of action and ability to delay loss of walking ability.

The advice applies only in the context of an approved NHS Scotland Patient Access Scheme, which the SMC said delivers cost-effective results. Implementation will require intensive monitoring, increasing the frequency of medicine reviews compared with current practice of 6-monthly visits and annual blood tests.

The SMC advice was welcomed by Duchenne UK as a “significant breakthrough” for patients in Scotland. The charity’s chief executive Emily Reuben called for the treatment to be “urgently approved” for use in England and Wales by the National Institute for Health and Care Excellence.

https://www.medscape.com/viewarticle/smc-approves-givinostat-duchenne-patients-scotland-2025a1000z1m