ITF Therapeutics, the U.S. affiliate of Italfarmaco, has announced publication of positive long-term safety and efficacy data for givinostat as a treatment for Duchenne muscular dystrophy (DMD) from the company’s open-label extensions of its Phase 2 and Phase 3 (EPIDYS) trials.
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The results, published in Annals of Clinical and Translational Neurology, show that long-term treatment with givinostat, a novel histone deacetylase (HDAC) inhibitor, in combination with corticosteroids, delayed disease progression in ambulant patients aged six years and older with DMD. Importantly, clinical benefit was observed across treatment groups receiving givinostat, with positive impact on key mobility functions such as rising from the floor, climbing stairs, and the ability to walk (ambulation). Givinostat has received marketing authorisation in the U.S., E.U. and U.K.
“These data represent an important step in building a robust body of evidence for the longterm use of givinostat in DMD,” said Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco. “The sustained benefit observed across functional outcomes reinforces the potential of givinostat to meaningfully alter the course of the disease. With its well-established safety profile and ease of administration, givinostat continues to emerge as a valuable treatment option for patients affected by DMD and their families.”
The study included multiple cohorts of boys with DMD all of whom received givinostat over various durations. Some had previously taken part in the Phase 2 or Phase 3 EPIDYS studies - either on active treatment or placebo - before entering the extension study. Others enrolled directly into the extension study after meeting eligibility criteria while not participating in the main trial. The total treatment exposure for some patients exceeded eight years.
“For patients and families affected by Duchenne, maintaining motor function for as long as possible can mean more independence, more participation, and more time doing everyday activities that matter,” said Scott Baver, PhD, vice president, medical affairs at ITF Therapeutics. “Our new long-term data further reinforce the potential of our treatment option to make a real difference for patients.”
Using propensity matching methods, 142 patients receiving givinostat and 142 from the natural history cohort were included in the analyses. In individuals who began treatment with givinostat in EPIDYS or the long-term extension study, patients treated with givinostat experienced a delay in disease progression compared to the matched natural history cohort. The data suggest that givinostat may delay the loss of the ability to rise from the floor by a median of 2.0 years, loss of the ability to climb four stairs (4SC) by 3.3 years, and loss of the ability to walk by 2.9 years. These findings further support the potential of givinostat to provide clinical benefit to patients with DMD. Givinostat was generally well-tolerated across all cohorts in this open-label extension study, and no new safety signals emerged during longterm treatment.
“These new findings show that treatment with givinostat continues to have a positive impact by addressing symptoms that patients are most concerned about, and that these long-term benefits are achieved over several years while treatment remains safe and tolerable,” added Craig M. McDonald, chair, Department of Physical Medicine & Rehabilitation, Professor, Departments of Pediatrics and Physical Medicine & Rehabilitation, University of California Davis Health, Sacramento, CA.