5 DMD Candidates to Watch in 2025

For patients with Duchenne muscular dystrophy, the last decade has been a fruitful landscape of progress. Eight drugs have been approved in the last eight years—including Sarepta’s Elevidys as the first gene therapy for the life-limiting neuromuscular disorder—yet the need for effective treatments remains high.

“With regulatory certainty came investment. With investment came medicines,” Paul Bolno, CEO of Wave Life Sciences, told BioSpace. However, “There’s still a massive unmet need. Even with the gene therapy approval, we still haven’t seen what durability looks like.”

Bolno expressed optimism that the current landscape is ripe for further innovation. “When the community, physicians, companies and regulators work together to establish a very precedented path forward, it drives people to make more medicines,” he said.

Multiple companies are digging in to add the next generation of exon skippers, gene therapies and medicines targeting more than skeletal muscle to their DMD pipelines, and for Michael Kelly, chief scientific officer of CureDuchenne, 2025 is shaping up to be a pivotal year.

“I think ‘25 is going to be quite distinguishing for a number of companies,” Kelly told BioSpace. A nonprofit venture organization, CureDuchenne invests in many of the biotech companies working in this space, including Sarepta, Avidity Biosciences, Capricor Therapeutics and Dyne Therapeutics.

DMD is a complex disease, Kelly said, requiring a full toolbox of treatment options, from gene therapies to anti-inflammatory drugs and immunosuppressants. “There’s a lot of components needed to treat this.”

With the treatment market for DMD projected to expand from $2.2 billion in 2023 to $7.4 billion by 2034, there is plenty of room at the innovation table.

Here are some of the top contenders Kelly—and BioSpace—are keeping a close eye on this year.

First up is Capricor’s allogeneic cell therapy, which already has a Biologics License Application under FDA review for DMD cardiomyopathy.

An off-the-shelf therapy, deramiocel is made from donor hearts. Capricor extracts a very specific cell, expands it in the lab and administers it to patients with DMD four times a year via intravenous infusion. The therapy is anti-inflammatory, immunomodulatory, antifibrotic and pro-regenerative, meaning it drives the patient’s natural cell processes toward repair, CEO Linda Marbán told BioSpace. So far in Phase II studies, deramiocel is slowing disease progression in non-ambulatory patients by almost 50% in terms of loss of upper limb performance, compared to natural history studies.

“But the most important mechanism of action is the fact that we see slowing of decline in cardiac function, which is typically what takes many [patients’] lives,” Marbán said.

If deramiocel is approved, it will be the first therapy to specifically treat DMD cardiomyopathy. The leading cause of death from DMD, nearly all patients develop this condition by adulthood. Capricor has submitted for full FDA approval based on agency feedback, which is unique in the DMD space where most drugs have been approved under the FDA’s accelerated approval program. Marbán anticipates a PDUFA date to be set around September, potentially allowing for a fourth-quarter launch. The company is currently expanding its manufacturing footprint to enable the treatment of thousands of patients.

Dyne is currently recruiting for a pivotal trial of its next-generation exon 51 skipper, Dyne-251, for which it plans to pursue accelerated approval—based on FDA feedback—with dystrophin expression as a surrogate endpoint.

In September 2024, the company announced Phase I/II data comparing Dyne-251 head-to-head with Sarepta’s exon 51 skipper Exondys 51, the current standard of care. First-generation exon skippers like Exondys 51 have difficulty getting inside the cell, Kelly explained, limiting the amount of exon skipping that can be accomplished and resulting in a low percentage of dystrophin expression.

In the Dyne-251 treated group, dystrophin expression was more than 10-fold higher. When adjusted for muscle content, this group reached nearly 9% mean absolute dystrophin. “It’s some of the best exon skipping data that we’ve seen at exon 51,” Kelly said.

Improvements were also recorded across multiple functional endpoints in the trial, and the drug demonstrated a favorable safety profile with no serious adverse events. With its registrational expansion cohort now underway, data are expected by the end of this year.

After reflecting on the needs of the patients, Wave determined that better cell delivery for more dystrophin generation and consistent expression was the ticket to a more effective therapy, according to Bolno.

At the six-month interim analysis in a Phase II study, Wave’s WVE-N531—an exon 53 skipper—showed 9% dystrophin expression consistently across patients. This translated to reduced blood levels of creatine kinase—a biomarker for muscle damage—and healthier looking muscles, Bolno said. Wave expects to deliver full 48-week data in the first quarter of 2025, which will include impact on clinical measurements.

If approved, WVE-N531 would be amenable to 8-10% of Duchenne patients. Wave has already begun preliminary work on potential therapies targeting exons 51, 52, 45 and 44.

Avidity is targeting an exon for which there are currently no approved drugs—exon 44—potentially opening up treatment for the approximately 6% of DMD patients who are amenable to exon 44 skipping.

In a Phase I/II trial, delpacibart zotadirsen (del-zota), increased dystrophin production to a whopping 25% of normal function in DMD patients—some of the best exon skipping data seen from any drug, according to Kelly. Del-zota also reduced creatine kinase to near the normal range.

Additional data are expected this year from the Explore44 open-label extension study as the company plans for a BLA submission around mid-2026. The FDA has already awarded del-zota orphan drug designation and fast-track status.

Some of the additional anticipated data from the next-gen exon skippers this year are expected to transform the exon skipping space, Kelly said. These newer products target all tissue—including the heart and diaphragm—which is not the case for currently approved drugs.

“I think we’re going to see some transformative therapies this year and approved the following year,” he said.

Regenxbio is chasing down Sarepta’s Elevidys in the gene therapy space with RGX-202, currently in a pivotal phase study.

The trial is enrolling 30 patients aged 1 year and older, representing an overall younger population than Elevidys’ current label. Early results reported in November 2024 from a small number of patients were “extremely encouraging,” Kelly said, with a strong safety profile accompanied by improvements in strength and time function tests. Regenxbio expects to submit a BLA in 2026.

A key challenge for gene therapy in this space is the size of the DMD gene, which is simply too large for the AAV delivery vehicle, Kelly said. Therefore, a truncated version is utilized, but its product cannot act at the full efficiency of the full-sized protein. Regenxbio’s design allows for a slightly larger version of the gene than Elevidys.

Kelly is looking forward to seeing the data from an earlier trial expanded to a larger number of patients. If successful, he believes it will add another opportunity and another choice for parents who are looking for a DMD gene therapy.