In his first earnings call just days after becoming Sarepta Therapeutics' CEO, Michael Severino recognized that the rare disease drugmaker faces multiple upcoming milestones to clarify its growth trajectory.
While Sarepta’s second quarter was, in Leerink Partners analysts’ words, “largely uneventful,” the company is approaching several make-or-break moments in the near future.
For its bread-and-butter Duchenne muscular dystrophy business, Sarepta just wrapped up a high-profile regulatory battle with the FDA around the gene therapy Elevidys, only to find itself gearing up for another one centered on its exon-skipping regimens Vyondys 53 and Amondys 45.
“We recognize that concerns around Elevidys adoption, competition on the horizon for exon-skipping treatments, and capital allocation remain,” Severino said on Sarepta’s earnings call Wednesday. “However, we are prepared to meet these challenges.”
Elevidys’ sales in the second quarter dropped 4% sequentially to $98 million, although they came 3% ahead of Wall Street’s expectations.
In a positive sign, Severino pointed to an increased number of patient enrollment forms as “providing early evidence that our expanded commercial initiatives are taking hold.”
“Our focus is now on execution, improving patient identification, expanding education for patients and families, and continuing to strengthen healthcare providers’ confidence to drive demand,” Sarepta Chief Commercial Officer Patrick Moss said on the call, adding that his sales team delivered a record number of interactions with doctors during the quarter.
However, because it takes a long time from patient expression of intention to actual infusion, the improvement is not expected to reflect in Sarepta’s revenue until 2027, Moss said. Given the lag, the company expects Elevidys revenue in the second half of 2026 to be “modestly lower” than in the first half, which benefited from a bolus of patients who lined up for infusion after the FDA expanded the gene therapy’s label in 2024, he explained.
Sarepta is rebuilding trust with doctors and patients after several liver safety-related patient deaths first led to a full halt to Elevidys treatment last year before the FDA relented and instead limited the gene therapy’s indication to ambulatory DMD patients only.
In one of the upcoming milestones flagged by Severino, Sarepta expects to finish enrollment this year into cohort 8 of the Endeavor study, which is assessing prophylactic sirolimus as part of an enhanced safety protocol for using Elevidys in nonambulatory patients.
Patients will be followed for 72 weeks, but Sarepta plans to speak with the FDA upon an early 12-week readout, which is now expected in the first quarter of 2027, a slight delay from the previous year-end 2026 timeline. The study’s primary endpoints include incidence of acute liver injury and Elevidys dystrophin expression at 12 weeks. Results from the study might be able to put Elevidys back in the FDA’s good graces in the nonambulatory Duchenne population.
Meanwhile, Sarepta’s exon-skipping DMD therapies also face significant uncertainties, even though their second-quarter sales of $231 million largely met analysts’ consensus.
After missing the primary endpoint of a confirmatory trial, Vyondys 53 and Amondys 45 are up for an FDA decision by Feb. 28, 2027, as Sarepta still hopes to turn their accelerated approvals into full nods. For now, the agency has not communicated any intent to schedule an advisory committee, Severino confirmed on Wednesday’s call.
In another threat, Dyne Therapeutics’ next-generation exon 51 skipper, zeleciment rostudirsen, a potential direct competitor to Sarepta’s Exondys 51, is under FDA priority review with a target decision date of Jan. 21, 2027.
During the investor call, Severino expressed a “tremendous amount of confidence in the durability” of the exon-skipping franchise, which boasts 10 years of commercial record since its first approval.
“We think any impact that competition would have would likely take some time to become visible,” the new Sarepta CEO said. “One has to overcome a number of hurdles when one enters a market like this.”
Severino pointed to reimbursement pathways and patient assistance programs that need to be established to ensure high rates of adherence.
Last year, Sarepta pivoted its R&D focus to siRNAs. As Severino and Leerink analysts noted, upcoming phase 1/2 readouts from its siRNA programs in myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy type 1 will be the key focus for Sarepta this year.