- Recommendation is based on Phase 3 EPIDYS trial data that demonstrated Duvyzat (givinostat) provides statistically and clinically meaningful treatment benefits in individuals with Duchenne muscular dystrophy (DMD)
- If approved by the European Commission, Duvyzat will be available for individuals with DMD aged six years and older who are able to walk; adding to the existing authorisations, already granted in the US and UK
- European Commission decision on marketing authorisation is expected in July 2025
MILAN, Italy, April 25, 2025 – Our partner Italfarmaco S.p.A. announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the granting of a conditional marketing authorisation for Duvyzat® (givinostat), a novel histone deacetylase (HDAC) inhibitor. The recommended marketing authorisation is for the treatment of patients with Duchenne muscular dystrophy (DMD) aged six years and older who are able to walk (ambulant), and taken together with corticosteroids. Conditional approval would make Duvyzat available to patients while Italfarmaco continues to generate additional clinical evidence to further strengthen and expand upon the compelling results observed to date. The European Commission (EC) will review the CHMP’s recommendation and is expected to make a final decision in July 2025. Pending authorisation, Italfarmaco will work closely with local authorities to facilitate rapid access, ensuring Duvyzat is made available across the European Union (EU).
The positive CHMP decision is based on the results of the EPIDYS Phase 3 multicentre, randomised, double-blind, placebo-controlled trial (NCT02851797). In the EPIDYS study, a total of 179 ambulant boys six years of age or older received either Duvyzattwice daily or placebo, in addition to corticosteroid treatment. The EPIDYS study met its primary endpoint demonstrating a statistically significant and clinically meaningful difference in time to complete the four-stair climb assessment.
Duvyzatalso showed favourable results on key secondary endpoints including North Star Ambulatory Assessment (NSAA), and fat infiltration evaluation by magnetic resonance imaging. Specifically, Duvyzat treatment was associated with 40% less decline in cumulative loss of NSAA items, indicating Duvyzat’s potential to delay disease progression in affected individuals. Most adverse effects observed with Duvyzatwere mild to moderate in severity. Results from this study were published in The Lancet Neurology in March 2024.1 Long-term data from the ongoing EPIDYS extension study was presented at the MDA conference, showing that givinostat may delay disease progression. Using propensity score matching, the median age at loss of ambulation was 18.1 years in the givinostat group versus 15.2 years in controls.2
In March 2024, the US Food and Drug Administration (FDA) approved Duvyzat for the treatment of patients aged six years and older independent of ambulation status, and in December 2024, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) granted full approval for ambulant patients six years and older, while conditional approval was given for non-ambulant patients.
In compliance with the paediatric investigational plan (PIP), Italfarmaco is conducting two additional clinical studies to determine the safety and efficacy in non-ambulant patients with DMD nine years of age and older (NCT 05933057), and to assess the safety and potential benefits of early treatment in patients with DMD two to five years of age (NCT 06769633). These studies are an integral part of Italfarmaco’s efforts to generate additional evidence and to expand the understanding of Duvyzat’s full therapeutic potential across the broad spectrum of disease progression with the goal of ensuring access for all individuals affected by DMD, regardless of age or functional status.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the DMD gene. Mutations in the DMD gene prevent the production of functional dystrophin, causing the dystrophin-associated protein complex (DAPC) to break down. This makes muscle fibres more vulnerable to damage and increases histone deacetylase (HDAC) levels in the muscle cells, blocking the activation of important genes needed for muscle maintenance and repair. As a result, muscle fibres experience ongoing damage, leading to chronic inflammation and poor regeneration. Over time, muscle cells die and are replaced by scar tissue and fat.3, 4-6 DMD primarily affects males, with symptoms typically appearing between the ages of two and five. As the condition progresses, muscle weakness worsens, leading to difficulty walking and eventually to loss of ambulation. Over time, the heart and respiratory muscles are also affected, which are the leading causes of premature death.7 DMD is one of the most severe and common forms of childhood muscular dystrophy, with a global birth incidence of approximately 1 in 5,050 boys.8
About Duvyzat®
Duvyzat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Duvyzat® is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. 9,10
References:
1. Mercuri, E, Vilchez, JJ, Boespflug-Tanguy, O, Zaidman, CM, Mah, JK, Goemans, N. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2024;23:393-403.
2. Vandenborne, K., McDonald, C., Servais, L., Munell, F., Schara, U., Bertini, E., Comi, G., Blaschek, A., Cazzaniga, S., Bettica, P. U., & Mercuri, E. (2025, March). Givinostat in Duchenne muscular dystrophy: Effect on disease milestones [Poster presentation]. MDA Clinical & Scientific Conference, Dallas, TX.
3. Sandonà M, Cavioli G, Renzini A, et al. Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies. Int J Mol Sci. 2023;24(5):4306. doi.org/10.3390/ijms24054306.
4. Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL. Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases. Mol Med. 2011;17(5):457–465. doi.org/10.2119/molmed.2011.00049.
5. Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023;14:1183101. doi.org/10.3389/fphys.2023.1183101.
6. Giuliani G, Rosina M, Reggio A. Signaling pathways regulating the fate of fibro/adipogenic progenitors (FAPs) in skeletal muscle regeneration and disease. FEBS J. 2022;289(21):6484–6517. doi.org/10.1111/febs.16080.
7. Walter MC, Reilich P. Recent developments in Duchenne muscular dystrophy: facts and numbers. J Cachexia Sarcopenia Muscle. 2017;8(5):681–685. doi.org/10.1002/jcsm.12245.
8. Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. 2020;15(1):141. doi.org/10.1186/s13023-020-01430-8.
9. Comi G, Bertini E, Vita G, et al. S22.008: Development of the histone deacetylases inhibitor Givinostat in Duchenne Muscular Dystrophy. Poster. Neurology. 2018;90(15 (Supplement)).
10. Licandro SA, Crippa L, Pomarico R, et al. The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene. Skelet Muscle. 2021;11(1):19. doi.org/10.1186/s13395-021-00273-6.
