Duchenne muscular dystrophy (DMD) is a rare, progressive genetic disorder characterized by the loss of functional muscle tissue, primarily affecting boys. Caused by mutations in the dystrophin gene, DMD leads to muscle weakness, loss of ambulation, and, eventually, life-limiting complications involving the heart and respiratory system. In recent years, advances in gene therapy, exon-skipping therapies, and novel pharmacologic approaches have begun to reshape the treatment landscape, offering new hope for patients and families.

One of these treatments is DUVYZAT (givinostat), a novel histone deacetylase (HDAC) inhibitor. Recent data from ITF Therapeutics’ open-label extension of the Phase 2 and Phase 3 (EPIDYS) trials indicate that long-term treatment with givinostat, in combination with corticosteroids, may delay disease progression in ambulant patients aged six years and older. The findings, published in Annals of Clinical and Translational Neurology, show that patients receiving DUVYZAT experienced slower declines in key mobility functions, such as rising from the floor, climbing stairs, and walking, compared with a matched natural history cohort. Some patients in the study received treatment for more than eight years, and no new safety concerns were identified during long-term follow-up compared to the natural history cohort.

DUVYZAT has now received approval from the FDA, the European Commission, and the UK’s Medicines and Healthcare products Regulatory Agency. DDN spoke with Scott Baver, Vice President and Head of US Medical Affairs at ITF Therapeutics, to discuss these findings and the evolving DMD treatment landscape.

How has the Duchenne treatment landscape changed over the past decade?

There have been many important and highly encouraging advances in research and medicine related to DMD and other forms of muscular dystrophy in recent years. Only 10 years ago, steroids were the standard of care for DMD, and there were not as many options for patients. Today, the treatment landscape has expanded significantly as multiple treatment options, including DUVYZAT, have become available. We are excited to join with the DMD community in calling for continued support for research that can lead to additional treatments in the years ahead.

DUVYZAT is a HDAC inhibitor. Could you explain how this mechanism contributes to muscle repair and anti-inflammatory responses in DMD?

HDACs are enzymes located in the body’s cells that play a key role in maintaining and repairing muscle tissue by modifying proteins that regulate muscle fiber repair pathways. In DMD, HDAC is overactive. Increased HDAC activity, in combination with the structural instability of dystrophin-deficient muscle cells, disrupts the normal muscle repair process and accelerates tissue deterioration.

While the exact mechanism is unknown, DUVYZAT is believed to work by targeting HDAC overactivity, which leads to increased muscle fiber repair and regeneration, decreased inflammation, and reduced adipogenesis and fibrogenesis. The most common side effects of DUVYZAT included diarrhea, nausea, vomiting, stomach pain, low platelet counts, increased fat levels in the blood, and fever.

We’ve seen gene therapies, exon-skipping agents, corticosteroids, and now HDAC inhibition all enter the picture. What does this wave of therapeutic diversity mean for patients?

Therapeutic diversity is extremely important for the Duchenne community because not every treatment has been proven to benefit every patient. The progressive nature of Duchenne sometimes means that patients of different ages and stages of disease require different treatment methods, but all of them are in urgent need of care. With more options available, clinicians are better able to customize treatment for each patient.

What are the benefits of DUZYVAT as a treatment for patients with DMD?

The regulatory review and approval of DUVYZAT in the US was based on Italfarmaco’s multi-year clinical development program, including results from the pivotal Phase 3 EPIDYS study. In the EPIDYS study, a total of 179 ambulant boys six years of age or older received glucocorticosteroid treatment, and either DUVYZAT twice daily or placebo. The EPIDYS study met its primary endpoint, demonstrating that patients treated with DUVYZAT showed a statistically significant and clinically meaningful difference in time to complete the four-stair climb assessment.

From what you’ve heard, how does a two- or three-year delay in disease progression change the way families plan for the future?

The passage of time is often associated with loss of muscle and ultimately loss of muscle function for patients affected by Duchenne. Maintaining muscle function for as long as possible can mean more independence, more participation, and more time doing everyday activities.

A two- or three-year delay in disease progression can have significant implications on the way families plan for the future.
– Scott Baver, Vice President and Head of US Medical Affairs at ITF Therapeutics

From what we’ve learned during our interactions with patients and families, a two- or three-year delay in disease progression can have significant implications on the way they plan for the future. For patients with Duchenne, delaying disease progression can help them maintain their independence and continue participating in the everyday activities that they enjoy. We hope that this delay allows patients and families to make plans for the future with less fear and uncertainty.

You’re launching a real-world evidence study. What do you expect to learn from it that clinical trials couldn’t capture?

As is the case with most clinical trials, our past studies were conducted in a carefully controlled environment in order to determine whether DUVYZAT was safe and effective. Study participants were selected based on strict eligibility criteria, including age, functional status, and other factors.

The goal of our 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. This study will enable us to gather data from a broader, more diverse population with insights into the impact of treatment on their daily lives. Our hope is that this study will give us a better understanding of the full potential of DUVYZAT.

Where do you think the field is headed in the next five to ten years — is the goal functional stabilization, extending ambulation, or potentially making Duchenne a manageable condition?

Since ITF Therapeutics was launched in January 2024, we’ve learned from the Duchenne community that “urgent” is an understatement when describing the need for additional treatments to slow or stop the decline caused by DMD. There is so much hope and promising research on the horizon. And for all patients and families, advances that can help them retain function, extend ambulation, and help to transform Duchenne into a manageable condition will represent significant advances in care.

With so many new therapies emerging, what advice would you give families trying to navigate treatment choices?

With more options available, it is especially important for patients and families to work closely with their medical care teams when making treatment decisions. Families should review data on safety and efficacy for different treatments. Fortunately, patients and families can now access information from multiple sources, including advocacy groups and pharmaceutical companies. For example, ITF Therapeutics launched the ITF ARC (Access, Resources and Care) program, which offers support that helps make insurance coverage navigation easier, helps address patient financial concerns, and encourages adherence to therapy.

This interview has been condensed and edited for clarity.