With a clutch of key data and planned regulatory applications this year from Avidity Biosciences, REGENXBIO and Capricor Therapeutics, CureDuchenne CSO Michael Kelly sees “momentum” in the Duchenne muscular dystrophy pipeline, as Sarepta’s Elevidys leaves the door open.
After a year marked by uncertainty surrounding Sarepta’s Elevidys and subsequent questions about AAV vector safety, the Duchenne muscular dystrophy community is on the cusp of the next generation of treatments for the neuromuscular disease.
“I am really thrilled to see the culmination of a lot of our work over the last two decades come forward,” Debra Miller, founder and CEO of the advocacy group CureDuchenne, told BioSpace, pointing to three potential new therapies expected to hit the FDA’s desk this year, from REGENXBIO, Capricor Therapeutics and Avidity Biosciences, picked up by Novartis last October for around $12 billion.
CureDuchenne has contributed funds to Capricor, Avidity, Sarepta and Dyne Therapeutics.
Sarepta’s Elevidys, which was tagged with a black box warning for severe liver injury and acute liver failure after the deaths of two teenage patients, is currently the only gene therapy on the market for DMD. However, with competitors like REGENXBIO and Solid Biosciences coming to the fore, Sarepta may not maintain its stranglehold on the market for long.
For Michael Kelly, chief scientific officer at CureDuchenne, the sector’s trajectory is set for success. “We’re seeing momentum build into the pipeline,” he told BioSpace.
Avidity plans to file a Biologics License Application (BLA) this quarter for exon-skipper del-zota. After receiving a complete response letter in July 2025 for deramiocel in DMD cardiomyopathy, Capricor was vindicated with positive Phase 3 results for its investigational cell therapy—currently under FDA review—in December. And REGENXBIO is gearing up to report pivotal topline data in the second quarter from its gene therapy RGX-202—a potential competitor to Elevidys—followed by a planned BLA in mid-2026. Solid is in Phase 1/2 studies with its gene therapy, SGT-003.
Another potential application could come from Dyne for zeleciment rostudirsen (z-rostudirsen), in development for patients with mutations in the DMD gene that are amenable to exon 51 skipping. In a December readout from a Phase 1/2 trial, the therapy delivered what Stifel analysts called the “best ever” functional improvements for an exon-skipper in DMD. A Phase 3 trial is set to kick off in the second quarter, and Dyne is “on track” to submit for accelerated approval, according to the company’s December press release.
“There’s a whole plethora of opportunities that are developing at a right pace right now,” Kelly said. “I think the next 12 months will be incredibly exciting [and in] the next 24, we’ll see another handful of drugs approved.”
Novartis Bets on Avidity’s Exon 44-Skipper Del-zota
Del-zota, an antibody-oligonucleotide conjugate (AOC) in development for patients with DMD who have gene mutations amenable to exon-44 skipping, clearly caught the attention of Novartis.
The acquisition announcement—2025’s second-largest buyout—came less than two weeks after Avidity reported the conclusion of a “positive” pre-BLA meeting with the FDA regarding its planned filing for del-zota. The meeting “was highly collaborative and provided a clear path forward for our BLA submission,” Sarah Boyce, the company’s president and CEO, said in a statement at the time.
Avidity is targeting an accelerated approval for del-zota, but is preparing a confirmatory study to support full global approval of the drug, according to the October 2025 press release.
Avidity in September touted positive results from Phase 1/2 studies of del-zota, which reversed disease progression and elicited positive functional improvements in patients after one year of treatment. Analysts at BMO Capital Markets said in September that they expect the current lack of approved exon-44 skipping treatments to lead to a smooth BLA submission and approval for the candidate.
Capricor’s Deramiocel Back at FDA After Positive Phase 3
2025 was a rollercoaster for Capricor, which in July was hit with a surprise rejection for its investigational cell therapy deramiocel. The drug, still under consideration by the FDA pending more information from the company, is in development for cardiomyopathy associated with DMD—a condition that CEO Linda Marbán previously told BioSpace “is what typically takes a patient’s life.”
In the complete response letter, the regulator said Capricor’s data package failed to demonstrate deramiocel’s effectiveness. This was a surprise to Marbán, who spoke of “positive interactions” with the FDA during the company’s second quarter earnings call in August.
The rejection came after Center for Biologics Evaluation and Research director Vinay Prasad canceled a previously scheduled advisory committee meeting for deramiocel—one that had been scheduled by Nicole Verdun, former director of the FDA’s Office of Therapeutic Products who was ousted that same month.
In December, however, the horizon cleared for Capricor when the cell therapy aced the pivotal Phase 3 HOPE-3 trial. Deramiocel hit the trial’s primary endpoint, showing statistically significant benefits in upper-limb function, along with the key secondary endpoint, demonstrating a decline in cardiac function as measured by left ventricular ejection fraction.
Last month, the FDA requested the clinical study report from HOPE-3 and supporting documents as part of the review process, which Marbán last week told BioSpace the company is working “literally around the clock” to prepare. Capricor plans to submit these materials by the end of February. Providing the FDA accepts the documents, deramiocel’s file will be opened, and as a class 2 resubmission, will be evaluated within six months.
Marbán said Capricor applied for a Commissioner’s National Priority Voucher for deramiocel but has not heard back. “We’re going to try again,” she said, adding that the CNPV “seems to be a program that doesn’t have a clearly defined pathway.”
REGENXBIO Seeks To Challenge Elevidys With RGX-202
REGENXBIO is gearing up to bring the second gene therapy to the market for DMD.
In June last year, the Maryland-based biotech reported interim Phase 1/2 data for its candidate RGX-202, demonstrating consistent, robust expression of microdystrophin, a shortened version of the dystrophin gene that is mutated in DMD, according to a press release at the time. The data came from five patients, aged 6 to 12 years, tracked for 9 and 12 months post-treatment.
BMO analysts characterized the results as being largely in line with Sarepta’s Elevidys.
“Although certain [RGX-202] functional improvements appear slightly higher than Elevidys, given the high variability across patients/control and lack of placebo arm, we don’t think the efficacy difference between RGNX/Elevidys is material or could drive/prove differentiated clinical outcomes,” they wrote in a June 5 note to investors.
RGX-202 delivers a novel microdystrophin that includes the functional elements of the C-terminal (CT), which is found in naturally occurring dystrophin, according to the biotech’s website. The presence of CT in preclinical studies has been shown to recruit a number of key proteins to the muscle cell membrane, eliciting improved muscle resistance in dystrophic mouse models.
In an R&D update on Jan. 11, REGENXBIO announced long-term functional data for four children with DMD who are able to walk and were treated with the planned pivotal trial dose of RGX-202. All participants exceeded expected disease trajectory on a key measure of motor function, according to the company.
Like Avidity, REGENXBIO is also seeking accelerated approval of its candidate in mid-2026, at which time the company expects to have most of its pivotal trial enrolled. As of June 2025, REGENXBIO was targeting approval of RGX-202 in the first half of 2027.
Solid Bio Targets Accelerated Pathway for Differentiated Gene Therapy
Coming up behind REGENXBIO is Solid Biosciences with its DMD gene therapy SGT-003, currently in a Phase 1/2 clinical trial.
In a Jan. 13 pipeline update, the biotech reported that as of the Jan. 9 safety cutoff date, SGT-003, which contains a “differentiated microdystrophin construct,” has been “generally well tolerated” in the 33 participants dosed in the ongoing INSPIRE DUCHENNE trial.
In February 2025, Solid reported biopsy data from the first three participants in the trial, showing an average microdystrophin expression of 110%.
Part of what differentiates SGT-003, CEO Bo Cumbo said, is Solid’s proprietary, next-generation capsid, AAV-SLB101, which was designed to target integrin receptors. The capsid has shown enhanced cardiac and skeletal muscle transduction with decreased liver targeting in nonclinical studies, according to the company’s website. AAV accumulation in the liver was responsible for the deaths of the patients taking Elevidys.
A second key aspect of the program is SGT-003’s transgene, which Cumbo said has a “unique structure.” It includes the R16/17 domain, meaning it can recruit for proteins that Solid believes “will make a profound difference long-term in these patients.”
Craig McDonald, chair of the Department of Physical Medicine & Rehabilitation at UC Davis Health and a principal investigator on Solid’s Phase 1/2 trial, said that targeting this domain “has huge impacts on both blood flow to the muscle as well as the potential to improve fibrosis.”
McDonald told BioSpace he is encouraged that transgenes such as Solid’s “might be associated with greater endurance with physical activity [and] less fatigue” in patients with DMD.
Solid aims to secure a path this year to accelerated approval, Cumbo said, and in a “perfect storm,” begin a rolling BLA submission by the end of 2026.
Of the overall DMD treatment landscape, Cumbo told BioSpace, “I’m very hopeful that we can make real progress over the next couple years.”
Sarepta Opens Study Testing Pretreatment in Non-Ambulatory Patients
Sarepta has already crossed its first big catalyst of 2026—reporting three-year data late last month from the Phase 3 EMBARK trial testing Elevidys in ambulatory patients.
Patients receiving the gene therapy saw their disease progression slow by 73% in terms of time-to-rise from the floor and 70% in the 10-meter walk-run measurement, according to the company’s Jan. 26 press release. Trial participants also saw improvements in motor function.
“Seeing the trajectory continue to widen over time and seeing the true benefit come out is just tremendous and gratifying,” Louise Rodino-Klapac, president of R&D and technical operations at Sarepta, told BioSpace.
McDonald concurred, saying that many of the patients he treated in the Elevidys clinical trials “are now four to five years out, and are doing extremely well.
“Certainly, the three-year data, I think, stacks up quite well with my clinical experience in seeing these patients have very different phenotypes and a very different disease course than what I’ve been seeing for 35 years of treating Duchenne dystrophy patients,” he continued.
Not everyone was as impressed, however.
“I don’t know if [Elevidys] works,” Mitchell Kapoor, senior analyst at H.C. Wainwright, told BioSpace earlier this month after looking at the data, as well as previous trial readouts of the gene therapy.
Sarepta is also testing the immunosuppression pretreatment sirolimus in 25 patients with DMD who are unable to walk in Cohort 8 of the Phase 1b ENDEAVOR study. The use of sirolimus is intended to mitigate the risk of acute liver injury. Shipments of Elevidys to nonambulatory patients were halted after the two Elevidys-linked deaths last year.
The first ENDEAVOR patient should be dosed “shortly,” a company representative told BioSpace in an email, with a readout expected at the end of the year.
“That’s going to be important,” Rodino-Klapac said, “because we really want to make sure we’re treating the entire population or getting to a point where we can treat the entire Duchenne population.”
No Cures
While the momentum and excitement in the DMD space are palpable, Cumbo pointed out that none of these treatments will bring a cure for DMD.
“We always need better products until this disease state is cured,” he told BioSpace last month. “My program is not going to cure kids with Duchenne, and other programs that are out there are not going to cure Duchenne, so realistically, until we find a cure, a true cure, we need to continue to innovate [and] create second-gen, third-gen programs.
“You don’t get to a cure when one company . . . dominates the landscape,” Cumbo continued. “Physicians need choice. Patients need choice.”
McDonald wouldn’t go as far as to use the word cure, but he did suggest the potential for patients with DMD to one day have a similar life expectancy to people with Becker muscular dystrophy, a less severe and slower-progressing disease. The average life expectancy for patients with BMD is 67 years, he said.
“I actually think we can get to a point where we have transformational changes that allow these patients to have near-normal life expectancies.”
Rodino-Klapac was also hesitant to use the word. “We have a lot of hope that there will be a cure someday, but I’m very cautious about using the word cure, especially for a genetic disease like Duchenne,” she told BioSpace. “In my mind, you would have to fix the genetic mutation in every single cell,” which is a “high bar.”
The next step for Rodino-Klapac is enabling earlier treatment. “What we know, even from our own studies, is that the earlier you treat the better,” she said, explaining that by doing so, fibrosis and muscle break-down is stopped in its tracks. This objective got a boost, she said, when the Department of Health and Human Services added DMD to the country’s newborn screening panel in December.
“We’re going to have earlier identification. Patients can get treated shortly after birth, and then that really will change this disease forever.”
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.