Givinostat is a new drug from the Italfarmaco Group that has demonstrated its safety and efficacy to treat Duchenne muscular dystrophy (DMD) in children, in the EPIDYS phase 3 clinical trial, the results of which have been presented by the Corporate Medical Director of the Italfarmaco Group , Dr. Paolo Bettica, at the PPMD (Parent Project Muscular Dystrophy) Annual Conference on June 25.
Duchenne muscular dystrophy is a genetic disease that causes progressive muscle weakness and degeneration. It is due to the presence of mutations in the DMD gene that result in a lack of dystrophin, a key protein in maintaining the structural and membrane stability of muscle fibers. It mainly affects males and its symptoms usually begin to manifest between two and five years of age. Over time, patients lose the ability to walk, and it subsequently affects the heart and respiratory muscles, causing premature death. The incidence of DMD is approximately one in 3,500-6,000 male live births worldwide.
The main objective of the study was to assess the efficacy and safety of Givinostat – the company’s patented histone deacetylase (HDAC) inhibitor – in slowing disease progression in 179 children with muscular dystrophy of the Duchenne patients with a mean age of nine years, who retained the ability to walk and had been on stable steroid treatment for at least six months. Participants were divided into two groups, which received Givinostat oral suspension or placebo for 18 months.
One and a half years after treatment with Givinostat, boys with Duchenne muscular dystrophy had less progression of their disease and showed greater agility
When 18 months passed from the start of treatment, the children who received Givinostat had less disease progression than those who received a placebo. Patients treated with this medication maintained greater agility to climb four steps (a test used to assess the progress of the disease), taking 1.78 seconds less than the others. Better results were also obtained when measuring biological markers of disease progression, such as infiltration of adipose tissue in the vastus lateralis muscle of the thigh. The data indicated that Givinostat treatment delayed fat infiltration by approximately 30%.
The drug has also demonstrated its safety and tolerability, since most of the adverse effects that were observed were mild or moderate (95%). Three (2.5%) of the children treated with Givinostat discontinued the trial due to an adverse event. Adverse effects that occurred in at least one in 10 participants were diarrhoea, abdominal pain, thrombocytopenia, hypertriglyceridemia, decreased platelets and increased triglycerides.
Eugenio Mercuri, Professor of Child Neuropsychiatry at the Catholic University of Rome, stated that “the results obtained show the beneficial effect of Givinostat in boys with Duchenne muscular dystrophy and show its ability to slow down the progression of the disease.”
Givinostat helps slow muscle deterioration
In this new clinical trial, Givinostat has continued to demonstrate a tolerability profile in line with previous studies. In fact, this drug has already received orphan drug designation from the FDA and the EMA (European Medicines Agency). Now, based on the results obtained, which show that the addition of Givinostat to steroid treatment provides clinical benefits for the study patients, Italfarmaco plans to meet with the US and European Union regulatory bodies to discuss the possibility to submit a marketing request. In addition, its intention is to present the full results of the EPIDYS study for publication in a peer-reviewed scientific journal.
“These key results from the Phase 3 clinical trial in DMD add to the growing body of data we have collected in recent years showing positive results with our investigational therapeutic candidate, Givinostat, co-administered with steroids in DMD patients, providing new hope for boys with DMD, their families and the scientific community”, said Dr. Paolo Bettica.
“There is a huge unmet medical need for new medicines to treat this debilitating rare disease and with these positive results, we intend to meet with regulatory agencies to share these findings and discuss the way forward to bring the full set of data to market. a marketing request for possible approval. We are excited to share these positive new tests from the EPIDYS trial with the community and would like to thank everyone involved,” he concludes.
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