Health Canada speeds up its review of givinostat for Duchenne
The oral therapy, known as Duvyzat in the US, could be approved by year's end
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Health Canada has accepted and granted priority review to Italfarmaco’s application seeking the approval of oral givinostat, sold in the U.S. under the brand name Duvyzat, to treat Duchenne muscular dystrophy (DMD).
The priority review status is reserved for therapies that could significantly improve the benefit-risk profile over current treatments. This designation shortens the evaluation to a 180-day target, meaning a regulatory decision could come before the end of the year, according to a company press release.
The mechanics of DMD and current treatments
“Health Canada’s acceptance of the [application] for givinostat with Priority Review is an encouraging step forward,” said Francesco Di Marco, PhD, CEO of Italfarmaco Group. “As we expand our presence in Canada, we are committed to working with clinicians, patient organisations, and other stakeholders to support the Duchenne community and help advance access for appropriate patients, if approved.”
Italfarmaco announced it will establish a local Canadian affiliate to lead ongoing discussions with health authorities throughout the review process and to support patients, families, and healthcare providers.
In DMD, mutations in the DMD gene disrupt the production of dystrophin, a protein that helps protect muscle fibers from damage. Without it, muscle fibers experience ongoing damage, inflammation, and poor regeneration, and are gradually replaced by scar tissue and fat.
Current guidelines recommend treatment with immunosuppressing corticosteroids from the onset of symptoms. While these medications can slow or stop muscle breakdown, they cause a wide range of side effects, especially if taken long-term. Several DMD-specific treatments are available in the U.S., but not in Canada.
“Families affected by Duchenne muscular dystrophy in Canada currently have limited access to treatment options that can slow functional decline,” said Jean K. Mah, MD, director of the pediatric neuromuscular program at Alberta Children’s Hospital in Canada.
Givinostat is designed to inhibit histone deacetylases (HDACs), enzymes that are abnormally elevated in DMD-affected muscle cells and prevent the activation of genes required for muscle maintenance and repair. By suppressing excessive HDAC activity, givinostat helps restore those repair processes, regardless of the specific DMD mutation.
The oral therapy has already received regulatory approvals in the U.S., the U.K., the European Union, and the United Arab Emirates for DMD, with additional regulatory submissions ongoing in other regions.
Italfarmaco’s application is supported by data from the EPIDYS Phase 3 trial (NCT02851797), which evaluated givinostat against a placebo in 179 boys with DMD, ages 6 to 17, who were able to walk.
The study met its primary goal, demonstrating a clinically meaningful difference in the time required to complete a four-stair climb assessment. Boys treated with givinostat twice daily, in addition to corticosteroids, performed better on this test than those receiving the placebo plus corticosteroids.
EPIDYS participants continue to be followed in a long-term, open-label extension (OLE) study (NCT03373968) assessing efficacy and tolerability, with follow-up extending up to 11 years. OLE results published last year showed that long-term treatment with givinostat delayed the loss of key motor skills in DMD boys.
The most common treatment-related adverse events occurring in at least 10% of participants were decreased platelet counts (cell fragments that help blood clot), increased blood triglyceride levels (fats), diarrhea, and abdominal pain.
None of the severe or serious adverse events were considered treatment-related. Tolerability was managed through monitoring and dose adjustments, and no other safety concerns were observed.
“As a clinician treating DMD patients, I am encouraged by this positive step in the Canadian regulatory progress and givinostat’s therapeutic potential demonstrated in the EPIDYS Phase 3 study,” added Mah, who was an investigator for the EPIDYS and OLE studies.
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