Long-term Duvyzat helps maintain motor skills in Duchenne MD
Results show therapy has potential to 'meaningfully alter' disease course
Long-term treatment with Duvyzat (givinostat) delays the loss of key motor skills in people with Duchenne muscular dystrophy (DMD), published results from an open-label extension study show.
“The sustained benefit observed across functional outcomes reinforces the potential of Duvyzat to meaningfully alter the course of the disease,” Scott Baver, PhD, head of U.S. medical affairs at ITF Therapeutics, said in an interview with Muscular Dystrophy News Today.
The results were published in the Annals of Clinical and Translational Neurology, in the study, “Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons.”
“These new findings show that treatment with [Duvyzat] 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,” Craig M. McDonald, MD, a study investigator, and chair and professor at the University of California Davis Health, said in a company press release.
What is Duvyzat?
Duvyzat is approved for DMD in people, ages 6 and older. It blocks the activity of histone deacetylases, enzymes that regulate gene activity. Available data indicate it helps reduce inflammation, scarring, and fat infiltration into muscles. The drug’s approval was mainly based on data from the Phase 3 EPIDYS clinical trial (NCT02851797), which tested it against a placebo in 179 boys with DMD who could walk and were on corticosteroids. They were later able to enroll in a long-term extension study (NCT03373968) where all the participants are taking Duvyzat.
The extension study also includes those given Duvyzat in a Phase 1/2 trial (NCT03238235) and some who were screened, but weren’t assigned to treatment or the placebo in EPIDYS. The published analysis includes 194 patients treated for a mean of 559.6 days, or about 1.5 years. The maximum treatment duration was more than eight years, including Duvyzat’s use in prior studies.
Comparing the findings from the long-term study against natural history studies that assessed the disease trajectory without treatment (except for corticosteroids), Duvyzat delayed the loss of patients’ ability to walk, climb a short set of stairs, and rise from the floor.
“These data suggest that treatment with Duvyzat may delay the loss of motor function, further supporting the potential of the drug to provide clinical benefit to patients with Duchenne,” Baver said.
The motor function gap that favors Duvyzat over the natural history group started around age 10. According to Baver, “maintaining muscle function can mean patients can live with higher levels of independence and spend more time doing everyday activities.”
Measuring respiratory function
The extension study also evaluated changes in respiratory function, using forced vital capacity (FVC) and peak expiratory flow (PEF) as measures. FVC tracks how much air can be exhaled in a forceful breath, while PEF measures how quickly air is exhaled.
Over the follow-up, FVC percent declined, but PEF percent remained largely unchanged. “This suggests that while lung capacity declined over time, patients’ ability to exhale forcefully did not show a significant decrease during the study,” said Baver, who noted that, compared with “matched historical controls, the decline in FVC was less pronounced in participants treated with Duvyzat over the same time period.” The existing data are still too limited to know Duvyzat’s effect on later-stage disease milestones, such as the need for a tracheostomy, wherein a small opening is made in the neck so a tube can be inserted directly into the windpipe, he said.
As shown at the Muscular Dystrophy Association Clinical & Scientific conference, two years after patients lost their ability to walk, the average FVC score was higher for those given Duvyzat than with the natural history study.
Studying Duvyzat
Most participants reported at least one adverse event, mostly mild to moderate in severity, without unexpected safety issues.
The extension study also included nonambulatory patients who completed the EPIDYS trial, but the results here varied. To better understand Duvyzat’s effects in this patient population, Italfarmaco (which includes ITF Therapeutics) is running the Phase 3 study ULYSSES trial (NCT05933057) in boys with DMD, ages 9-17. Its primary goal is to assess the efficacy of Duvyzat at reducing muscle decline, as measured by Performance of the Upper Limb 2.0. The therapy’s safety and tolerability are also being evaluated, along with its efficacy, including with respiratory function.
“We hope that the ULYSSES trial will provide more insights regarding how Duvyzat can help slow disease progression, specifically in the nonambulant population, which is a patient group that has historically had fewer research-driven treatment options,” Baver said.
Also, the observational PROVIDUS study (NCT07127978) will evaluate safety and efficacy in DMD patients who are starting Duvyzat or have initiated it recently. The study will also include participants in gene therapy and exon-skipping therapies.
“The goal of this real-world evidence study is to complement findings from our clinical trials and provide a more comprehensive understanding of Duvyzat’s real-world performance and the overall patient experience,” said Baver, who noted that although the data so far reinforce the drug’s safety and efficacy, ITF will continue working with “members of the patient, caregiver, and advocacy communities to advance research that can provide more insights on the impact of treatment with Duvyzat.”
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