Deramiocel in Duchenne muscular dystrophy: Phase 3 trial results and cardiac outcomes

In addition, as patients live longer and transition into adulthood, cardiac complications are becoming more prominent. There are currently no Duchenne muscular dystrophy (DMD)-specific cardiac therapies. We rely on medications used in other cardiomyopathy settings, such as ACE inhibitors, based on data from those trials. However, these are not tailored specifically to DMD.

Another challenge is the transition to adult care. There is still limited awareness among adult specialists, and there are not enough coordinated, multidisciplinary care models to manage these patients effectively as they age.

Could you explain deramiocel’s mechanism of action and why it may be particularly relevant in DMD?

There can sometimes be confusion, but this is not a stem cell therapy. It is a cardiosphere-derived cell therapy, meaning the cells are derived from heart muscle tissue.

These cells have anti-inflammatory and anti-fibrotic properties. We know that inflammation plays a key role in DMD, which is why we use steroids. Over time, both skeletal and cardiac muscle become fibrotic. The rationale is that targeting inflammation and fibrosis could help slow disease progression, which is why this approach is being explored in DMD.

Could you explain the study design and key findings from the trial, and describe what makes them especially important from a cardiac outcomes perspective?

There have been preclinical and open-label data, but the most recent findings presented at the American Academy of Neurology Annual Meeting are from the HOPE-3 trial, a phase 3 randomized, placebo-controlled study over 12 months.

The study included boys aged 10 years and older, both ambulatory and non-ambulatory, and focused on upper limb and cardiac function. One important aspect is that it included non-ambulatory patients, who are often underrepresented in clinical trials.

From a results perspective, there was a statistically significant difference between the treatment and placebo groups in the Performance of Upper Limb (PUL) score, favoring the treatment group and indicating a slowing of disease progression. This is particularly notable, as it is one of the first studies to demonstrate a significant improvement in upper limb function in this population.

In terms of cardiac outcomes, the ejection fraction remained stable in the treated group compared with expected decline based on natural history and placebo data, which suggests a potential benefit in preserving cardiac function.

The study also incorporated the Duchenne Video Assessment, a novel, home-based functional assessment where daily activities are recorded by caregivers and scored by trained therapists. This approach may provide more qualitative insight into functional changes compared with traditional clinic-based measures. One component of this assessment also showed a statistically significant benefit in the treatment group.

Were there any patient subgroups who appeared to derive greater benefit, and how might that help clinicians think about future treatment sequencing or selection?

The study focused on older boys, including those who are late ambulatory or non-ambulatory. The applicability to younger patients will depend on regulatory approval and the final prescribing information.

In clinical practice, if the therapy is approved and safety data support it, there may be interest in using it in younger patients, although this would need to be approached cautiously.

From a cardiac perspective, use will likely depend on the approved indication. There may also be potential for preventive use, similar to how we use other cardiac medications, but again, this would depend on safety data.

In terms of real-world use, we are increasingly moving toward combination therapies in DMD. This therapy could potentially be used alongside gene therapies or exon-skipping therapies, as the mechanisms are different.

If approved, how do you envision deramiocel being integrated into the existing Duchenne treatment landscape alongside steroids, exon-skipping therapies and emerging gene-based approaches?

It will likely be individualized based on the patient, payer coverage, and the approved label. Since this is a cell therapy, it must be administered in specialized infusion centers with the appropriate infrastructure, which is an important practical consideration.

More broadly, as combination approaches become more common in DMD, therapies with different mechanisms of action, such as deramiocel, could be used as add-on treatments alongside existing options.