- Regulatory approvals in the US and UK; EMA evaluation ongoing
- Additional Phase II/III trials underway in Europe and Canada to further assess safety and efficacy in a broader patient population
- Italfarmaco remains committed to its global commercialization strategy to address unmet medical need in Duchenne muscular dystrophy
MILAN--(BUSINESS WIRE)--Italfarmaco S.p.A. today announced a comprehensive update on the regulatory and clinical advancements for givinostat, the company’s drug for the treatment of Duchenne muscular dystrophy (DMD). The update highlights key regulatory milestones and ongoing clinical trials.
Regulatory Milestones
Givinostat has been granted regulatory approval in the US (March 2024) and the UK (December 2024), marking critical milestones in the global effort to make the therapy available to patients. In the UK, givinostat was granted full approval for ambulant patients six years and older, while conditional approval was given for non-ambulant patients. In the US, full approval was granted for patients six years and older regardless of their ambulatory status, further emphasizing the treatment’s potential across the disease spectrum.
The European Medicines Agency (EMA) is currently reviewing the Marketing Authorisation Application (MAA), with a Committee for Medicinal Products for Human Use (CHMP) opinion expected in the first half of 2025. Regulatory filings in additional countries are actively progressing as part of Italfarmaco’s commitment to global patient access.
Carlos Barallobre, CEO of Italfarmaco, said, “At Italfarmaco, our unwavering commitment is to the Duchenne community. The givinostat approvals in the US and UK, along with the promising long-term data we are generating, bring us closer to our goal: ensuring that every patient, regardless of location, has access to a therapy that can make a difference in disease progression. We are diligently working with global regulatory bodies to expedite availability, because we understand that for patients and families affected by DMD, every moment counts.”
Ongoing Clinical Trials in DMD
Three clinical trials are currently underway in Europe and Canada, designed to expand the potential use of givinostat and to provide long-term follow up on treated patients:
- NCT05933057: Evaluating non-ambulant patients aged 9 years and older
- NCT06769633: Evaluating pharmacokinetics and safety in younger patients aged 2 to 5 years, with recruitment recently completed for the first cohort of 4- to 5-year-olds
- NCT03373968: Confirming long-term tolerability and efficacy of givinostat treated patients, with up to eleven years follow-up
Paolo Bettica, MD, PhD, Chief Medical Officer at Italfarmaco Group, stated, “Our continuing clinical trial evaluation seeks to further affirm givinostat’s clinical value in Duchenne muscular dystrophy, where treatment options remain limited, and by precisely targeting the biological drivers of muscle degeneration. We look forward to our ongoing interactions with the regulatory bodies and thank the clinicians for their tireless efforts and the DMD community and families for their continuing trust.”
About Duchenne Muscular Dystrophy
DMD is a progressive neuromuscular disorder caused by a mutation in the DMD gene which affects the production of a protein called dystrophin.3 Dystrophin is a critical component of the dystrophin-associated protein complex (DAPC) which supports the strength, stability, function and repair of muscle cells. In DMD, muscle fibres are highly susceptible to injury and this continuous muscle injury leads to chronic inflammation, impairment of muscle regeneration and muscle replacement by fibrotic and fat tissue.4, 5-7 The disease primarily affects boys, with symptoms usually first seen between two and five years of age. Symptoms worsen over time affecting the ability to walk. Eventually, heart and respiratory muscles are affected, which are the two main causes of premature death.8 DMD is one of the most severe and common forms of childhood muscular dystrophy, with a worldwide birth incidence of around 1 in 5,050 boys.9
About Givinostat
Givinostat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Givinostat is an orally administered histone deacetylases (HDAC) inhibitor. HDAC is activity upregulated in DMD muscle and has the potential to modify the expression of certain genes and biological processes involved in muscle repair and inflammation.10, 11
About ITALFARMACO
Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 60 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialisation with proven success in many therapeutic areas including immuno-oncology, gynaecology, neurology, cardiovascular disease and rare diseases. Italfarmaco’s rare disease unit includes programmes in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythaemia vera.
References:
- 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.
- 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. Supplementary appendix. Lancet Neurol. 2024;23.
- Ryder S, Leadley RM, Armstrong N, et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis. 2017;12(1):79. doi:10.1186/s13023-017-0631-3
- 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. https://doi.org/10.3390/ijms24054306.
- 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. https://doi.org/10.2119/molmed.2011.00049.
- Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023;14:1183101. https://doi.org/10.3389/fphys.2023.1183101.
- 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. https://doi.org/10.1111/febs.16080.
- Walter MC, Reilich P. Recent developments in Duchenne muscular dystrophy: facts and numbers. J Cachexia Sarcopenia Muscle. 2017;8(5):681–685. https://doi.org/10.1002/jcsm.12245.
- 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. https://doi.org/10.1186/s13023-020-01430-8.
- 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)).
- 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. https://doi.org/10.1186/s13395-021-00273-6.
Contacts
Media enquiries:
Anja Heuer / Jacob Verghese |+49 (0) 151 106 199 05 | italfarmaco@trophic.eu
Other enquiries:
Patient Advocacy and Communications Lead| s.parker@italfarmacogroup.com
