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Italfarmaco’s Newly Approved Nonsteroidal Therapy Givinostat Already Helping Boys with Duchenne Muscular Dystrophy (DMD)

ORLANDO, Florida — Until Susan Caldwell of Waxahachie, Texas, learned in 2016 that her 8-year-old son Ryan Michael had Duchenne muscular dystrophy (DMD), she had never heard of the disease—and only vaguely knew of muscular dystrophy, thanks to the Jerry Lewis Telethon.

“It was devastating,” she recalled. “I had met with his regular pediatrician because Ryan Michael couldn’t stand up like a normal kid. I didn’t know there were different kinds of muscular dystrophy or that there was a treatment for it until I walked down this path. I was heartbroken.”

Ryan Michael was referred to pediatric neurologist Diana Castro, MD, who at the time was codirector of the Muscular Dystrophy Association (MDA) Care Center at University of Texas-Southwestern Children’s Hospital in nearby Dallas.

“She walked us through Duchenne and what its possible outlooks were. She talked about power chairs and different types of steroids,” Caldwell said. “We decided to put him on deflazacort (Emflaza®). Within a few months, our insurance gave us the approval, so we started him on that.”

But soon after, Caldwell learned of an upcoming trial for givinostat—a potentially less damaging alternative to deflazacort—and concluded that it might be a good fit for her son, who has an exon 74 deletion. The closest location offering givinostat treatment was at the University of Iowa MDA Care Center in Cedar Rapids, under the direction of Katherine Mathews, MD.

Caldwell said that shortly after Ryan Michael—now 16 and an official MDA Ambassador—enrolled in the trial, she became convinced he was receiving a placebo because his condition began to deteriorate before her eyes.

“He was falling 4 or 5 times a day. As the disease progressed, I was pretty sure he’d be in a wheelchair pretty soon,” she told Rare Disease Advisor. “But then in November 2019, he went on the medication, into the open-label portion. It was probably about 4 months in when I started really noticing changes. Before that, opening bottles was a challenge for him, and one day he opened a bottle and started drinking. It took me a second to register what was happening.”

But the most dramatic moment came during a recent trip to the neighborhood grocery store.

“We stopped to pick up water,” Caldwell said. “Ryan Michael walked ahead of me, picked up an 18-pack of 10-ounce bottles, and dropped it into the shopping cart. I was dumbfounded. This was right after givinostat got approved. I asked him to do it again so I could take a video.”


Third New DMD Treatment Approved in Less Than a Year

Results like this led the US Food and Drug Administration (FDA) on March 21, 2024, to approve givinostat (now marketed as Duvyzat™) for boys—making it the first nonsteroidal therapy for all variants of DMD and marking a big win for Italian drugmaker Italfarmaco.

Givinostat is a histone deacetylase (HDAC) inhibitor that changes gene expression in cells by altering the 3-dimensional folding of DNA. It represents a new mechanism of action for patients with the progressive neuromuscular disease.

This marks the third new treatment for Duchenne since June 2023, following the FDA’s approval of Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (Elevidys®) as the first gene therapy for DMD and vamorolone (Agamree®), which is marketed in the US by Catalyst Pharmaceuticals.


Matt Trudeau is general manager of ITF Therapeutics, the newly created US affiliate of Italfarmaco, based in Boston, Massachusetts. In an interview at the recent 2024 MDA Clinical & Scientific Conference in Orlando, Florida, he said givinostat is ITF’s first launch in the US.

“We’re building very quickly to live out the promise of givinostat initially for patients with Duchenne. Then, we hope to do more good from there in rare disease more broadly,” said Trudeau, a veteran of the rare disease industry who has worked with Genzyme, Biogen, and Bluebird Bio.

In the phase 3 EPIDYS clinical trial of 179 ambulant boys aged 6 or more years with Duchenne, givinostat showed “clinically meaningful and statistically significant” improvement in the time to climb 4 stairs between the treatment group and a placebo control group.

In addition, the company said, analysis of key secondary endpoints—including fat infiltration evaluation by magnetic resonance imaging and muscle function and strength tests—yielded results consistent with the primary endpoint.

“The wonderful thing about givinostat, as I look at it, is that it is not specific to a certain genotype. It has the potential to treat a broad cross‑section of patients with DMD,” Trudeau said. “We are energized by what we see from the clinical data. Just 10 years ago, steroids were the standard of care, and there wasn’t a lot of options for these patients. Today, there are multiple options for these patients. The pipeline is robust, and I think that’s great.”

Givinostat, a small molecule, is an oral solution taken with food twice a day. Side effects are minimal; in the phase 3 trial, clinicians observed slightly increased rates of thrombocytopenia, diarrhea, and hypertriglyceridemia.

“There is incredible innovation and discovery ongoing in HDAC inhibitors and in regulation of transcription. Givinostat is also an innovative approach to approaching Duchenne muscular dystrophy and is the next innovation for this space. The data bear that out,” Trudeau said.

“We’re very focused on bringing givinostat to patients in the US and doing right by communicating the data—both safety and efficacy—and also doing our very best to remove nonclinical barriers if the decision is being made to make sure patients can get access to therapy,” he added.


Double Approach Could Have Broad Reach

Patient advocacy groups are reacting enthusiastically to givinostat’s approval.

“As the Duchenne world has evolved, we’re now seeing many options that are generalizable for our community,” said Pat Furlong, president and CEO of Parent Project Muscular Dystrophy. “Givinostat adds to our toolbox in that the HDAC inhibitor is both anti-inflammatory and anti-fibrotic. This drug has both of those characteristics.”

Furlong said that at some point, givinostat may be useful in treating patients with Becker muscular dystrophy as well as female carriers of Duchenne.

“This adds to the list of approved treatments for families facing this devastating disease,” said Debra Miller, founder and CEO of CureDuchenne. “It’s an important step forward in accelerating transformative treatments for everyone, independent of their genetic mutation.”


Sharon Hesterlee, PhD, chief research officer at the MDA—which funded preclinical mouse studies of HDAC—said the approval of givinostat provides another significant treatment option for people with Duchenne, and that “as more drugs are approved for DMD, we look forward to understanding if and how they might be used in combination.”

Meanwhile, Caldwell said that her son—who’s attended MDA Summer Camp for 6 years and is engaged with the MDA Let’s Play community—is doing relatively well.

“I’m a single mom and I do it all. When he’s not in school, he’s pretty much with me,” she said, noting that while her son is still ambulatory, he uses a wheelchair at school. Unlike many boys with Duchenne, Ryan Michael is not overweight. “He’s 4-foot-3 and weighs only 60 pounds. He eats all day but doesn’t gain weight. I wish he had that problem.”



Miami native Larry Luxner, a veteran journalist and photographer, has reported from more than 100 countries in Latin America, Africa, Eastern Europe, the Middle East and Asia for a variety of news outlets. He lived for many years in San Juan, Puerto Rico, and the Washington, D.C., area before relocating to Israel in January 2017. Larry spent four years with BioNews Services writing news and features about the rare disease community from his base in Tel Aviv. He has continued his work covering rare diseases since joining Rare Disease Advisor in 2021.