A blood-based cell therapy slows muscle deterioration in children and young people with Duchenne muscular dystrophy, according to a phase III trial

HOPE-3 is the phase 3 clinical trial for Deramiocel. It is a systemic allogeneic cell therapy (based on cells derived from cardiospheres, or CDCs) that has been evaluated in participants with Duchenne muscular dystrophy (DMD) who are in the late ambulatory stage or non-ambulatory.

This is a very important finding, as few clinical trials target this population of patients with advanced Duchenne muscular dystrophy who are non-ambulatory or in the late stages of ambulation.

As demonstrated in this article, Deramiocel offers significant therapeutic benefits for both skeletal and cardiac muscle in advanced DMD, with manageable safety and tolerability.

In the context of DMD, Deramiocel does not correct the dystrophin deficiency in these patients, but it is capable of slowing the progression of the disease.

The therapeutic effects of Deramiocel are very encouraging:

• A 54% reduction in the mean progression of skeletal muscle disease over 12 months.
• With regard to the effects on the progression of cardiomyopathy, there was a 119 per cent slowdown in the average progression of cardiac disease, representing a stabilisation of cardiomyopathy progression not seen with other cardiac treatments for DMD.
• The preservation of upper limb function (the primary therapeutic objective in HOPE-3) yielded significant clinical benefits in advanced DMD. The indicators show an improvement in quality of life, taking into account the ability to eat independently (as reported by DMD patients) following treatment with Deramiocel at 12 months, which suggests a significant potential benefit in maintaining independence.

There are no approved specific therapies for cardiomyopathy in DMD, which is the leading cause of death in patients with this condition. The loss of dystrophin leads to inflammation and myocardial damage, which eventually results in the death of cardiomyocytes and their replacement by fibroadipose tissue. The stabilisation observed following treatment reflects the preservation of viable myocardium, resulting in the maintenance of overall contractile function.

Deramiocel significantly slows the progression of DMD with a favourable safety profile. Neither the preservation of upper limb function nor the attenuation of cardiomyopathy had previously been demonstrated in the population with advanced DMD. Another very important factor is that the study included DMD patients with various mutations; as this is a therapy that does not depend on the patient’s specific mutation, it is widely applicable.

These findings reinforce Deramiocel’s status as a safe, effective and promising therapy for people living with DMD, although longer-term follow-up is needed to establish its durability and long-term safety.

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder considered to be rare (1 in every 3,500–5,000 male births) caused by mutations in the DMD gene, which is responsible for the production of dystrophin, a protein essential for the stability and function of muscle fibres. It mainly affects males, as the DMD gene is located on the X chromosome, of which males have only one copy. The absence or deficiency of dystrophin causes progressive degeneration of the skeletal, cardiac and respiratory muscles, leading to a gradual loss of motor function and systemic complications.

Current therapeutic approaches include the use of corticosteroids to slow the progression of the disease, multidisciplinary supportive care (physiotherapy, rehabilitation, respiratory and cardiological support) and innovative molecular therapies, notably exon-skipping therapies, which aim to partially restore dystrophin production, and gene therapies, designed to introduce functional versions of the gene or microdystrophins into muscle cells. Furthermore, strategies based on gene editing and regenerative medicine are being investigated with the aim of improving muscle function and modifying the long-term course of the disease.

In this regard, the HOPE-3 clinical trial can be considered a cell therapy, as it involves the intravenous infusion of Deramiocel, a treatment based on a suspension of cells derived from allogeneic cardiospheres (CDC), meaning that these cells are derived from individuals other than the patient receiving the treatment. Furthermore, it should be noted that this is the first Phase III clinical trial to evaluate a non-autologous, systemically administered cell therapy for a genetic disorder, as well as the first Phase III registration trial conducted in patients with Duchenne muscular dystrophy (DMD) in the late stages of ambulation and in non-ambulatory patients.

In earlier phases of the trial, in addition to its safety and low toxicity, its efficacy had been verified not only in cardiac tissue but also in skeletal muscle, based on various parameters that were assessed. In this Phase III trial, which specifically measures clinical efficacy in a considerable number of individuals affected by the condition and which is published in the prestigious journal The Lancet, significant improvements were observed after 12 months of treatment in the treated patients compared with those receiving a placebo, for example in the PUL2.0 test, a validated scale for assessing upper limb function in patients with Duchenne muscular dystrophy.

It is particularly interesting that CDC exerts its effect on the target tissue, such as skeletal muscle and cardiac muscle, through the secretion of extracellular vesicles (nanometre-sized particles formed by a lipid bilayer and loaded with specific bioactive RNA), thereby exerting their anti-fibrotic properties and consequently slowing the progression of myopathy, muscle degeneration and the disease itself in general. Another noteworthy aspect of the study is that, unlike other therapeutic strategies which are specific to each mutation in the DMD gene, this approach is much more versatile, as it does not depend on the mutation carried by the affected individual; consequently, the number of patients who can be treated with this therapy is much greater.

In conclusion, it can be stated that this clinical trial, based on an innovative cell therapy, is a highly promising study yielding robust and significant results that reflect a slowing of the disease’s progression; whilst this does not, of course, constitute or can be considered a complete cure for the disease, it opens up a window of opportunity for patients with DMD.