Sarepta Therapeutics’ newly minted CEO Michael Severino laid out his path to returning the muscular dystrophy therapy maker to the forefront of the rapidly expanding market.
Sarepta Therapeutics’ new CEO Michael Severino has had 90 days to assess the path forward. With his Big Pharma lens, Severino thinks the biotech’s shift to effect size and quality clinical trials sites has set the muscular dystrophy therapy maker up to overcome the past few years of controversy.
During his first earnings call with the company on Thursday afternoon, Severino was asked for his opinion on Sarepta’s execution—given the biotech’s “mixed” history on clean clinical trial wins, as the analyst put it.
“One of the most important [things] is if you want to have a positive study, you need to have the most substantial effect size you can,” said Severino, who previously served in senior executive roles at AbbVie and Amgen.
Severino inherited a company that was emerging from a year of controversy. In 2025, multiple deaths were linked to Sarepta’s gene therapy programs, including the approved Duchenne muscular dystrophy (DMD) treatment Elevidys. Sales of the therapy spiraled as the benefit-risk profile was questioned.
In an attempt to move forward, Sarepta’s then CEO Doug Ingram signed a massive deal with Arrowhead Pharmaceuticals in November 2024, bringing in a new siRNA modality and mostly moving on from gene therapy.
Sarepta is also awaiting an FDA decision on the DMD exon skippers Vyondys 53 and Amondys 45. The company is seeking full approval of the treatments, which had each previously been granted accelerated approval by the FDA. But in November 2025, both failed confirmatory trials. Sarepta nevertheless resubmitted the package and a decision is expected in February 2027.
Enter Severino, with a tough job to do. He told analysts on Thursday that he’s satisfied with the work the company has been doing to improve clinical trials, including focusing on obtaining a bigger effect size to prove long-term benefit and better selection of clinical trial sites with the deep experience necessary to run a trial in a complex disease like DMD.
“I think we’ve gained significant experience as a company over the last many years in how to conduct studies in neuromuscular disease and how to pick those sites, and how to work with those sites to make sure we get quality data,” Severino said. “With respect to our study design and statistical capabilities, they are as good here as they are anywhere.”
The new CEO also expressed confidence in the upcoming siRNA programs from Arrowhead. Sarepta is preparing to initiate pivotal studies for SRP-1003 in myotonic dystrophy type 1 (DM1) and SRP-1001 in facioscapulohumeral muscular dystrophy (FSHD), both of which are expected to yield multiple ascending dose data by the end of this year.
“We know how to design studies well and I have a lot of confidence in the siRNA programs going forward, so I think we’ll put together the various pieces of what it takes to run a very effective and what I believe will be a successful registrational Phase 3 program,” Severino said.
Competitors on the horizon
After battling safety concerns in 2025, Sarepta now faces a new challenge: rival companies entering the DMD space. Dyne Therapeutics is expecting an FDA decision for zeleciment rostudirsen (z-rostudirsen), also an exon skipper, by January 21, 2027. Analysts from Oppenheimer said in July that the new treatment is likely to be approved and is poised to “capture the majority of market share.”
Z-rostudirsen, which is under review for patients with DMD who are amenable to exon 51 skipping, would go up directly against Sarepta’s Exondys 51.
“We’re prepared for that,” Severino said of the potential new rival. “We believe we are in a strong position to compete in a competitive marketplace.”
He pointed to a “very long track record of safety,” with demonstrated functional improvements, based on long-term, real-world data. Sarepta is also the long-time standard bearer in the DMD market, meaning the company already has the commercial presence and is well known to prescribers.
“It takes time in a marketplace like this to establish the appropriate commercial footprint, the reimbursement codes, navigate the reimbursement landscape, and that typically can take a period of months to several months,” Severino said. “Based on all those factors, we think wholesale switching of stable patients is not likely early on.”
But the competitor could begin to erode Sarepta’s market share in the second half of 2027, Severino admitted. “At this point, I think we need to see a little bit more, see what their label looks like before we give any more specific color, but that’s certainly the way we’re thinking about it.”
Severino will also have to work hard to recover Elevidys, with the gene therapy bringing in just $83.5 million in net revenue for the quarter. The value was above William Blair’s estimate of $81.5 million, but below consensus of $95.4 million and a significant drop from third quarter sales in each of the previous two years. The gene therapy brought in $131.5 million in Q3 2025 and $181 million in the same period a year earlier.
Still, analysts were encouraged by the Elevidys numbers, with William Blair noting that the business appears to be stabilizing.
“For the quarter, key leading indicators and enrollment forms for Elevidys were in line with the second quarter, demonstrating stabilization of the franchise,” the firm wrote on Friday morning. “The company indicated that it has seen an increase in the physician willingness to treat and families resuming their treatment journeys after pausing it.”
About 1,500 patients have been treated since the gene therapy’s June 2023 approval. Jefferies expressed confidence in sales rebounding in 2027 as Sarepta embarks on a marketing push.
Sarepta has collected a larger placebo-controlled dataset and established a benefit-risk profile for Elevidys and continues to work with the FDA to restore the non-ambulatory population to the gene therapy’s label, which was stripped last year amid the safety concerns.
The company said during its earnings call enrollment in the ENVISION study would not be resumed. The trial is focused on patients who are either non-ambulatory or aged 8 through 17 and was put on hold last summer after enrolling about half of the 150 goal. But Severino said the company plans to present the FDA with 12-week safety data from the non-ambulatory cohort of the ongoing ENDEAVOR study in the first quarter of 2027. This cohort is assessing whether giving a prophylactic sirolimus treatment before or after Elevidys can help reduce acute liver injury.
“Notwithstanding our decision to not resume enrollment in ENVISION, our commitment to serve non-ambulatory individuals with Duchenne remains steadfast,” Louise Rodino-Klapac, Sarepta’s top scientist, said on the call. “ENDEAVOR Cohort 8 remains central to this commitment.”
A potential label expansion aside, Elevidys is facing impending competition from REGENXBIO, which intends to file its investigational gene therapy RGX-202 with the FDA in the first quarter of 2027, according to the company’s Q3 update. The biotech is eyeing a potential accelerated approval in the second half of next year.
But Severino does not expect patients to wait for REGENXBIO’s approval to begin treatment.
“We know that these children have unfortunately a progressive, debilitating, and ultimately lethal condition, and that as time passes, there’s increasing muscle destruction that is irreversible,” the CEO said. “There really is an urgency to treat. And when there’s a fully approved product that has shown the long-term benefit that Elevidys has shown, we think that’s very meaningful to physicians and to patients and their families.”
Editor’s note (Nov. 6): This story was updated after publication to provide more detail on Sarepta’s studies of Elevidys use in non-ambulatory patients.
