Givinostat slows motor function loss in boys with DMD in trial: Results

Applications for approval of oral therapy now under review in US, EU

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

A pair of hands, a stethoscope and a handful of pills surround a graph showing measured improvements in a clinical trial.

Treatment with givinostat — an oral therapy currently up for approval in the U.S. and Europe — significantly slowed motor function loss among boys with Duchenne muscular dystrophy (DMD) in the Phase 3 clinical trial EPIDYS, according to the full study results.

Those results were detailed in a paper titled “Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial,” now published in The Lancet Neurology.

The work was funded by Italfarmaco, the company developing givinostat. The findings from the trial form the main basis of Italfarmaco’s applications seeking approval of givinostat for DMD, which are under review in the U.S. and the European Union.

“When managing DMD, a primary goal is to maintain motor function for as long as possible,” Craig M. McDonald, MD, a study author at the University of California Davis Health, said in a press release from the company.

“The results from EPIDYS provide robust evidence that givinostat has the potential to support this goal,” McDonald said.

Recommended Reading
Givinostat for Becker MD

Givinostat Appears to Slow Muscle Decline in Becker MD Trial

EPIDYS trial tested givinostat over 1.5 years in boys with Duchenne

Designed to reduce muscle wasting in DMD, givinostat works by blocking the activity of histone deacetylases (HDACs), a group of enzymes that regulate cellular genetic activity and are overactive in the disease.

“Givinostat has the potential, if approved, to benefit a broad DMD patient population independent of the underlying gene mutation,” said Eugenio Mercuri, MD, lead author of the study and a professor at the Catholic University, in Rome.

The EPIDYS clinical trial (NCT02851797) tested the therapy, at a dose of 10 mg twice daily, against a placebo for 72 weeks, for about 1.5 years. The study enrolled 179 boys with DMD, ages 6 through 17, all of whom were able to walk and were on a stable course of corticosteroids.

The trial’s main goal was to assess the impact of givinostat treatment on the time it took patients to climb four stairs. As previously reported, the results showed the decline was slower with givinostat than with the placebo, with a between-group difference of 1.78 seconds.

“Results of the four-stair climb assessment worsened in both groups over the study period; however, the decline was significantly smaller with givinostat than with [the] placebo,” the researchers wrote.

In addition to outperforming the placebo on the four-stair climb, givinostat also bested it on several secondary measures. Scores on the North Star Ambulatory Assessment, a 17-item assessment of motor function, declined by 40% less in patients given givinostat. The therapy also led to 30% less fat infiltration into thigh muscle, which predicts loss of ambulation and indicates disease progression, according to the company.

“The givinostat-treated group fared better than the control group in a range of muscle function and strength tests at 72 weeks,” Mercuri said.

Givinostat has the potential, if approved, to benefit a broad DMD patient population independent of the underlying gene mutation.

The most common side effects of givinostat seen in EPIDYS were decreased platelet counts, increased blood fat levels, diarrhea, and abdominal pain. These side effects were managed with monitoring and dose adjustments, and no treatment-related side effects were serious or severe.

According to McDonald, “taken together, these data suggest givinostat could be an effective new treatment for DMD management.”

Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco, called the full results of the trial “encouraging,” saying they “highlight the dedication of Italfarmaco’s research and clinical teams to achieve this milestone for the company,”

“We want to thank all the individuals and their families who participated in this international study and would also like to acknowledge the tireless efforts of the clinical investigators as well as the unwavering support of the DMD community,” Bettica said.