Analysts homed in on Duchenne muscular dystrophy and myotonic dystrophy type 1 assets during first quarter earnings as major players like REGENXBIO and Novartis as well as Dyne, Wave, Solid and Sarepta near the regulatory finish line.
Earlier this month, REGENXBIO added to the Duchenne muscular dystrophy picture with mixed pivotal data from its investigational gene therapy. Muscular dystrophies more broadly have anchored the headlines this past year, with Novartis’ $12 billion acquisition of Avidity Biosciences—2025’s second largest buyout—and last summer’s safety saga surrounding Sarepta Therapeutics’ Elevidys.
Moving into 2026, “I think the year started really well,” said Michael Kelly, chief scientific officer at CureDuchenne, a non-profit that invests in DMD-focused companies, including Dyne Therapeutics, Capricor Therapeutics and, formerly, Avidity. “There’s been a number of really important events that started to shape up both the first half and the second half of the year.”
Kelly listed the key recent and upcoming DMD catalysts in alphabetical order, starting with results from Avidity released about six weeks before Novartis swooped in. A Phase 1/2 trial of the exon-44-skipping therapy del-zota showed that biomarker improvements correlated with functional benefits, as assessed against a natural-history control. “Clearly, the Avidity data speaks for itself,” he told BioSpace.
Kelly then gave a nod to Capricor, which rebounded last fall from a surprise summer FDA rejection for deramiocel, in development for Duchenne muscular dystrophy cardiomyopathy. In December 2025, the biotech reported that the investigational cell therapy showed statistically significant benefits in upper-limb function, meeting the primary Phase 3 endpoint. Deramiocel is again under FDA review with an action date of August 22.
Finally, Kelly moved on to Dyne, which is planning an FDA submission for this quarter; REGENXBIO, which is eyeing a 2027 launch for the gene therapy RGX-202; and Wave Life Sciences, which confirmed in a Q1 report that a new drug application for exon-53-skipper WVE-N531 is on track for this year.
“Each of these companies have got data that’s new, and I think that each of them are in a position right now of FDA discussions or some clarity about PDUFA dates or wanting to file either a BLA or a new drug application this year,” Kelly said. “So that’s what the year is.”
It’s not all smooth sailing, though. In addition to the liver injury–related deaths of three patients linked to Sarepta’s gene therapy platform last year, the biotech’s exon skippers Amondys 45 and Vyondys 53 failed a confirmatory trial in November 2025. REGENXBIO has also had its fair share of challenges.
REGENXBIO’s mixed data creates doubt for near-term approval
Nothing has been easy this year for REGENXBIO. After failing to win FDA approval of its Hunter syndrome candidate in February, the biotech on May 14 reported two serious adverse events in the Phase 3 portion of a trial studying the DMD gene therapy RGX-202, spooking investors.
While the trial did meet its primary endpoint, with 93% of patients achieving at least 10% microdystrophin expression at week 12, the mixed data sent REGENXBIO’s stock falling 37%.
REGENXBIO attempted to position the readout as a win, however. Chief Medical Officer Steve Pakola said on a call the same day that correlation of microdystrophin expression and functional improvements has never been demonstrated before. He called this achievement a “landmark distinction” among DMD gene therapies. Sarepta’s Elevidys is currently the only gene therapy on the market for the disease.
But the two serious adverse events—along with regulatory uncertainty—threw a wrench into the celebration.
REGENXBIO reported one case of liver injury and one case of myocarditis, or inflammation of the heart. While the company said both events were “easily managed and resolved within weeks,” Leerink analysts told investors that the events “muddy the update.”
“Maintain[ing] safety is going to be really important, demonstrating efficacy is going to be important,” Kelly said prior to the data drop. The consideration for patients “is always about safety. They want to see safety; they want to see measures of efficacy.”
As for the regulatory picture, REGENXBIO had previously guided toward a mid-2026 submission for RGX-202 through the FDA’s accelerated approval pathway, with potential approval in the first half of next year. The May 14 announcement did not mention FDA submission plans, with the company stating only that the product is expected to be approved and launch in 2027.
DM1 readout could ‘mostly’ make or break Novartis’ Avidity buy
It was one of 2025’s biggest deals. Now, Novartis is about to learn whether the $12 billion buyout of Avidity last October was worth the risk.
Avidity came with a clutch of DMD and myotonic dystrophy type 1 (DM1) assets, a couple already nearing regulatory review. In September 2025, the biotech reported that exon-44-skipper del-zota reversed disease progression and improved functional outcomes in patients with DMD in two mid-stage trials. The company was expected to file for approval of del-zota in the first quarter.
On deck, Avidity is anticipating data from a Phase 3 trial of the DMPK-targeting therapy del-desiran in 159 patients with DM1 in the second half. The study is expected to complete in September, per ClinicalTrials.gov.
Oppenheimer’s Kostas Biliouris is focused on the trial’s primary endpoint, video Hand Opening Time (vHOT), a metric that he said is “very, very noisy.” Having analyzed baseline levels of vHOT across all of the DM1-focused companies Oppenheimer covers, “We see a very, very large variability across patients, across trials, and these can really impact your trial outcome,” he told BioSpace last month.
When asked whether this DM1 readout will make or break the acquisition, Biliouris said, “Mostly, yes. . . . This is perhaps 80% of the acquisition.” Based on Oppenheimer’s understanding, he added, “DM1 was the main driver of the acquisition.”
Del-desiran is a first-in-class and “perhaps the first ever DM1 drug that could potentially improve [the disease], which made it an attractive takeout target,” he said.
Kelly, however, disagreed with this singular focus. “I can’t believe that it’s going to make or break the $12 billion deal,” he said. “They bought a platform company and that platform is going to leverage a lot of opportunities into a whole bunch of diseases.”
Besides DMD and DM1, Avidity also has a candidate called del-brax in registrational trials for facioscapulohumeral muscular dystrophy.
Dyne reports positive pre-BLA meeting for exon 51 skipper
Analysts homed in on two assets following Dyne Therapeutics’ Q1 update: exon 51 skipper DYNE-251 (z-rostudirsen) for DMD and DYNE-101 (z-basivarsen) for DM1.
Acceptance of a BLA for DYNE-251 “is the next key catalyst” for Dyne, Oppenheimer analysts wrote in a May 11 note to investors. The biotech in its Q1 report described a “positive BLA meeting” with the FDA for the candidate, adding that a submission is on track for the second quarter, with a potential launch in Q1 2027.
“Continued supportive engagement with FDA is encouraging here after we saw mixed/negative confirmatory data from a few of SRPT’s exon skippers, even if those drugs are less efficacious than DYN-251,” Stifel analysts said in a May 11 note. On May 20, Dyne announced it had initiated the Phase 3 confirmatory trial for the asset. The 72-week trial will enrol around 90 participants.
As for DYNE-101, a global confirmatory Phase 3 trial is underway and Dyne has reached target enrollment of 60 patients, according to the report. However, individuals currently in screening who meet the trial’s criteria will be allowed to enroll. Dyne plans to reveal data from this cohort in Q1 2027 and is aiming to file for accelerated FDA approval early in the third quarter next year.
Solid’s safety profile a ‘meaningful competitive advantage’
Solid Biosciences has taken an important step forward in its development program for the DMD gene therapy SGT-003, with the first patient being dosed in a Phase 3 study, according to a May 7 announcement.
“We view dosing of the first patient in the Phase III IMPACT DUCHENNE trial as an important de-risking step that reinforces SGT-003’s path toward a registrational dataset and potential accelerated approval,” William Blair analysts wrote in a note the same day. “The transition into a randomized, placebo controlled, double-blind study marks a clear evolution from early signal generation to confirmatory evidence generation, which we view as essential in the current regulatory environment for Duchenne gene therapies.”
In February 2025, Solid reported biopsy data from the first three participants in a Phase 1/2 trial, showing that SGT-003 generated an average microdystrophin expression of 110%.
REGENXBIO’s recent data “reinforces microdystrophin as a surrogate, which is constructive for SLDB,” Jefferies wrote on May 14, adding, “RGNX’s functional data are promising and de-risking for SLDB but do not set a high bar, in our view,” the analysts added, as the study relies on external controls.
Part of what differentiates SGT-003 is Solid’s proprietary next-generation capsid, AAV-SLB101, which was designed to target integrin receptors, CEO Bo Cumbo told BioSpace in February. The capsid has shown enhanced cardiac and skeletal muscle transduction with decreased liver targeting in nonclinical studies, according to the company’s website.
In its May 7 update, Solid added that 46 patients in its Phase 1/2 trial have now been dosed with SGT-003 using a steroid-only prophylactic immunomodulation regimen, and that the gene therapy “has been generally well tolerated” as of the May 4 cut-off date.
“The absence of drug induced liver injury, myocarditis, thrombotic microangiopathy, and atypical hemolytic uremic syndrome across a growing dataset reinforces prior observations and continues to contrast favorably with programs requiring more intensive immunosuppression,” William Blair said.
Can Sarepta save its exon-skippers?
Rounding out this list is the current DMD market leader. From Biliouris’ perspective, Sarepta has two key upcoming catalysts.
The first is the FDA review of Amondys 45 and Vyondys 53. Sarepta confirmed in its Q1 report on May 6 that a supplemental new drug application has been submitted for the two drugs to the FDA seeking to convert their approvals from accelerated to full, despite their confirmatory flop.
In Sarepta’s Essence trial, launched in 2016 following the accelerated approval of both drugs, Amondys 45 and Vyondys 53 failed to significantly improve motor function in patients with DMD. Sarepta, however, blamed the miss on the COVID-19 pandemic, which it claimed “impacted study participants and outcomes.” When excluding data from patients who were tested for COVID, the company found a 30% reduction in disease progression over two years. While also not statistically significant, Sarepta deemed this to be a “clinically meaningful change.”
Sarepta’s other major event of 2026, Biliouris said, is an upcoming readout from a Phase 1b study testing the immunosuppressive regimen sirolimus during Elevidys treatment in 25 patients with DMD who are unable to walk. Biliouris expects these data in the fourth quarter.
Following the deaths last year of two patients in the non-ambulatory population, Elevidys is no longer indicated for this group. (The third death linked to Sarepta’s platform was in a trial for an investigational limb-girdle muscular dystrophy gene therapy.) Sarepta is now moving forward in a program designed to adapt Elevidys for use in these individuals.
As non-ambulatory patients account for half of all patients with DMD, a return to the market “could potentially double the revenue of Elevidys,” Biliouris said.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.