Application to market givinostat for DMD in Europe under review
Request comes after givinostat placed under priority review by US FDA
“Now that our market authorization application is under review, we are looking forward to working with the regulatory authorities to bring this treatment option to patients,” Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco, the company developing givinostat, said in a press release.
The submission came shortly after the U.S. Food and Drug Administration (FDA) placed a similar application under priority review, which should shorten the time for a decision from the standard 10 months to six.
“The acceptance of our submissions to European and U.S. regulatory bodies is a tremendous achievement for the company and reflects Italfarmaco’s research efforts and commitment to the successful clinical development of givinostat,” said Carlos Barallobre, Italfarmaco’s CEO.
Givinostat designed to block activity of enzyme called histone deacetylases
Givinostat is designed to block the activity of a type of enzyme called histone deacetylases (HDACs), which are involved in turning genes off within cells. These enzymes become overly active in people with DMD, contributing to symptoms such as muscle weakness and wasting.
By blocking HDACs, givinostat is expected to switch genes back on, including the FST gene, which codes for a protein called follistatin. This protein is expected to help build muscle mass while preventing fat and scar tissue from accumulating, thus easing muscle repair.
Both submissions were largely based on results from EPIDYS (NCT02851797), a company-sponsored Phase 3 clinical trial that tested givinostat against a placebo in 179 boys with DMD, ages 6-17 years, who were able to walk.
All boys, who were on treatment with Emflaza (deflazacort) or other oral corticosteroids for six months or longer, were randomly assigned on a 2-to-1 ratio to givinostat at a dose of 10 mg/mL or a placebo, given twice daily by mouth for 18 months.
The primary goal was to assess the change from the trial’s start to the end of treatment in the time needed to climb four stairs. Secondary goals included changes in other motor function measures, as well as evaluations of muscle strength, fat build-up in muscles, and side effects.
If approved, givinostat could greatly benefit younger and older DMD patients by preserving their motor skills and muscle strength.
Givinostat found to slow decline in motor function in boys with DMD
Results showed the treatment significantly slowed motor function decline, with boys given a placebo taking an average 1.78 seconds longer to climb four stairs than those on givinostat. Other measures of motor function also improved after 18 months on givinostat.
Treatment with givinostat also delayed fat build-up in the vastus lateralis, a muscle in the thigh, by about 30% compared with a placebo.
The most commonly reported side effects included diarrhea, abdominal pain, low platelet counts, and high levels of triglycerides, a type of fat. Most (95%) were mild to moderate in severity, with three boys discontinuing treatment with givinostat due to a side effect.
“The Phase 3 evaluation of Givinostat demonstrated that it can slow DMD progression in boys six years and older. If approved, givinostat could greatly benefit younger and older DMD patients by preserving their motor skills and muscle strength,” Bettica said.
Givinostat has received orphan drug designation for DMD from the EMA. It has also been given rare pediatric disease, orphan drug, and fast track designations by the FDA.