New treatment against Duchenne muscular dystrophy
Duvyzat can be used in a wide patient population from the age of six
NewsHumanMedicines
EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Duvyzat (givinostat) as a treatment for Duchenne muscular dystrophy (DMD) in patients from the age of six who are able to walk. Duvyzat is an oral suspension to be taken at the same time as corticosteroid treatment.
DMD is a rare genetic disease caused by a lack of dystrophin, a protein that helps strengthen muscle fibres and protect them from injury as muscles contract. This causes the muscles to progressively weaken and lose function and is ultimately lethal. This process is worsened by increased levels of histone deacetylases (HDAC), a class of proteins.
There is no cure for DMD and treatment is centred on corticosteroid therapy, prevention of contractures, and medical care of the heart and respiratory function.
The active substance of Duvyzat is givinostat, a histone deacetylase (HDAC) inhibitor that modulates uncontrolled HDAC activity in dystrophic muscles. Inhibiting HDAC activity may help to reduce inflammation and reduce tissue scarring and thickening.
The CHMP’s opinion is based on data from a subgroup of 120 patients (79 treated with givinostat and 41 with placebo) in a randomised, placebo-controlled study in ambulant DMD patients aged six years or older on concomitant steroid treatment. The primary endpoint was the change of time to complete a four stair climb (4SC), a tool widely used to assess motor function, at 18 months. The results were statistically significant, with the 4SC time increasing by an average of only 1.25 seconds in patients treated with givinostat compared to 3.03 seconds in the placebo group. The difference in the key secondary endpoints assessing function, strength and muscle morphology was not statistically significant, but all outcomes were more positive in patients treated with givinostat.
The safety profile of Duvyzat is based on data from 179 patients. The most common events in patients treated with givinostat were diarrhoea, abdominal pain, thrombocytopenia (low levels of blood platelets), vomiting, hypertriglyceridaemia (high blood levels of triglycerides, a type of fat) and fever.
Duvyzat is recommended for a conditional marketing authorisation, one of the EU’s regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.
In order to confirm the efficacy of Duvyzat, the company has been requested to conduct a randomised, placebo-controlled study in ambulant DMD patients and a post-authorisation efficacy and safety study based on data from a patient registry of children with DMD six years and older treated with givinostat.
The opinion adopted by the CHMP is an intermediate step on Duvyzat’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.
Notes
- The applicant for Duvyzat is Italfarmaco S.p.A.
- Duvyzat was designated as an orphan medicinal product on 04 July 2012 treatment of Duchenne muscular dystrophy. Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designations should be maintained.