The beginning to the year has been eventful in the Duchenne muscular dystrophy (DMD) space, with several trial readouts announced at the Muscular Dystrophy Association (MDA) 2025 meeting, which took place in Dallas, Texas from 16 to 19 March.
The sector was also shaken by the death of a patient who was dosed with Sarepta Therapeutic’s DMD gene therapy Elevidys (delandistrogene moxeparvovec), after experiencing acute liver failure.
Go deeper with GlobalData
Research by GlobalData estimates that across the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan), the market for DMD treatments is expected to rise from sales of $2.3bn in 2023 to $5.2bn by 2033. This is mostly driven by Elevidys and Santhera Pharmaceuticals’ Agamree (vamorolone).
GlobalData is the parent company of Clinical Trials Arena.
Capricor’s Hope-3
At the start of 2025, San Diego-based Capricor Therapeutics completed the submission of its Biologic Licence Application (BLA) for its stem cell-based therapy deramiocel (CAP-1002). The therapy is somewhat unique in that it consists of allogeneic cardiosphere-derived cells (CDCs) which have shown some pre-clinical ability to regenerative actions in dystrophinopathy and heart failure.
The ongoing Phase III Hope-3 study (NCT05126758) has recruited 104 non-ambulatory and ambulatory boys and young men with DMD to assess the treatment’s ability to restore upper limb mobility. The trial is due to complete on 1 December 2025.
Typically, DMD is a genetic disorder that causes progressive muscle weakness and wasting, primarily in young boys, due to a lack of the protein dystrophin. In turn, this has an impact on the cardiac system with cardiomyopathy manifesting as one of the leading causes of death among patients.
Discussing the DMD space with Clinical Trials Arena, attending physician at the Children’s Hospital of Philadelphia, John Brandsema commented that stem-cell treatment isn’t used anywhere else in the indication, making deramiocel unique.
Bransema said: “This is a population that has been traditionally harder to study, non-ambulatory patients with DMD. Motor outcomes in that group are less robust and less characterised.
“But encouragingly, the Phase II study did show an impact on the rate of decline in motor functional scale measured by the Performance of Upper Limb scale, so that in and of itself is an achievement because many DMD trials fail at the time of looking at primary outcome measures.”
Regenxbio’s Affinity
At the MDA conference, Regenxbio reported interim data from the Phase I/II portion of its Affinity Duchenne study (NCT05693142) that showed RGX-202 was able to induce a 122% microdystrophin expression in one child aged three.
The Phase I/II/III open-label study is evaluating the safety, tolerability, efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of RGX-202 in up to 65 patients. The trial has an estimated end date of 1 February 2026.
This therapy is designed to address the root cause of DMD by delivering a functional copy of the gene that encodes microdystrophin, making it a potential competitor to Elevidys in the US.
However, this part of the DMD space has a cloud cast over it after Pfizer’s Phase III Ciffero trial examining fordadistrogene movaparvovec failed to achieve its primary endpoint, and also led to a patient death in a Phase II study.
Brandsema added: “The idea of more is better is usually true in the context of dystrophin. The flip side of that is, is it functional? Is it doing what you’d like it to?
“You can make a lot of something in the cell, but if it’s not located where it’s supposed to be and interacting with the other proteins that it’s supposed to in a way that’s the most effective and functional, then you’re not going to see the benefit clinically.”
Sights on exon-skipping
GlobalData analysis shows that approximately $1bn of 2023’s DMD sales were products aimed at exon-skipping.
Exon skipping is one approach to treat DMD that involves using small, synthetic DNA molecules called antisense oligonucleotides (AONs) to skip specific sections of DNA, known as exons, during the process of RNA splicing. Theoretically this can prompt the body into producing dystrophin.
Avidity Bioscience’s Explore44-OLE trial (NCT06244082) is an open-label study examining its Exon 44 skipping therapy, del-zota, administered intravenously to DMD patients with mutations amenable to Exon 44 skipping. The trial is due to complete on 31 December 2025.
Approximately, 7% of the DMD population present with this mutation, meaning that there is a gap in the market for this specific variety of exon-skipping therapy.
Brandsema expanded: “This population is special because 44 skip amenable patients are usually on the milder end of the phenotype, although there are exceptions.
“The other biomarker in this trial that I took a strong impression from was the creatine kinase (CK) levels. There are a lot of patients who reject CK as a biomarker because it fluctuates so much in the natural state of this disease.
“It’s always very high but it may be about 30% higher or lower on the scale depending on the time you are measuring. However, these patients went to a normal CK level, something indistinguishable from normal healthy muscle tissue. So that’s very significant.”
Over in the EU
In Europe, NS Pharma is hoping that the European Medicines Agency (EMA) will give its exon-skipping therapy Viltepso (viltolarsen) the greenlight off the back of its Phase III Racer53-X trial (NCT04768062). The therapy has already received accelerated approval in the US.
The multi-centre, open-label extension study is evaluating the therapy in boys with DMD and is due to complete on 1 October 2025.
Due to its US accelerated approval, Viltepso looks to be a promising therapy in the DMD market for patients in Europe living with the exon 53 mutation.
GlobalData analyst, Asiyah Nawab, said: “The only caveat to this asset is the fact that it is specific to a certain population – those with exon 53 mutations. If approved, it is only limited to mainly ambulatory patients as key opinion leaders have expressed that it is not as effective in those that are non-ambulatory patients.
“Nonetheless, it would be the first exon-skipping therapy in the EU markets, having a good uptake.”
Nonsense mutations
PTC Therapeutics is attempting to reassert the safety and efficacy of its DMD therapy Translarna (ataluren) through a Phase III trial (NCT01247207) in patients with nonsense mutation dystrophinopathy.
Nonsense mutation dystrophinopathy affects approximately 10-15% of patients with DMD and is caused by introduction of a premature stop codon into a patient’s mRNA sequence, causing the production of truncated, non-functional, dystrophin.
The therapy received conditional marketing approval in 2014 from the EMA but a decade later in October 2024, the EMA recommended against renewing the marketing authorisation for Translarna, citing an inability to determine its effectiveness, pulling it from shelves across the continent.
Now, many expect the FDA to follow suit after the agency rejected New Drug Applications (NDA) for the therapy in 2016 and 2017.
Nawab added: “Key opinion leaders are excited about this asset due to data read outs and efficacy in patients. However, this asset has had a turbulent journey. The EMA has recently announced that they will not be renewing the license in the EU, with Germany having already withdrawn this asset.
“Since the FDA and EMA are two separate bodies, their decisions do not influence one another, hence this could see an approval. However, if the EMA has decided to not renew the asset and are pulling it from EU markets because it is not effective in patients, the FDA may also believe the same after review.”
PTC Therapeutics’s open-label study is estimated to have enrolled 270 patients and is due to complete on 31 April 2025.
