Sarepta Therapeutics CEO Doug Ingram opened the company’s first-quarter earnings call Tuesday by acknowledging that, like the broader biopharma industry, the genetic medicine biotech is facing a challenging time.
Following report of a patient’s death after treatment with Sarepta’s Duchenne muscular dystrophy gene therapy Elevidys, some families have paused the treatment process to seek additional information, Ingram said on the call.
Patient hesitation, coupled with a severe flu season and administrative delays at some treatment sites, caused Elevidys to miss sales expectations. The drug delivered $375 million in sales during the first quarter, a 2% sequential decline and 11% below analysts’ consensus estimate.
As a result of these trends, Sarepta’s Chief Customer Officer Dallan Murray warned that Elevidys’ sales in the second quarter could be as much as 20% lower than in the first quarter.
Sarepta has also dialed back its total 2025 revenue projection to a range between $2.3 billion and $2.6 billion exclusively because of lower Elevidys expectations, Ingram said. The company’s previous guidance was $2.9 billion to $3.1 billion, including $900 million in sales from its other DMD drugs Exondys 51, Vyondys 53 and Amondys 45.
However, Murray stressed that the company expects “only a temporary impact,” and that its long-term demand outlook for the one-time gene therapy “remains strong.” Ingram also noted that patient start forms are still coming in from both ambulatory and nonambulatory patients.
In March, Sarepta disclosed that a 16-year-old patient had passed away after developing acute liver failure following Elevidys treatment and a recent cytomegalovirus infection, which can infect and damage the liver. Elevidys, like other adeno-associated virus (AAV) vector-based gene therapies, comes with a liver toxicity risk. But the death was the first among more than 800 patients who have received the Duchenne therapy in clinical trials or in the commercial setting.
“We are continuing to explore what was uniquely different about this case than every of the other hundreds and hundreds of infusions that have occurred to date,” Ingram said.
The company has not received the autopsy report but expects it in the next month or two, according to Ingram.
Sarepta has submitted a request to the FDA to include the death case in Elevidys’ label, and the agency plans to review the situation by the end of the year, Sarepta’s R&D chief, Louise Rodino-Klapac, Ph.D., said on the call.
Data so far suggest no difference in the rates of adverse events in relationship to age or weight, Rodino-Klapac said. No relationships have been identified between liver safety signals and the total Elevidys dose administered, or patient age or weight.
Top experts in the DMD field have not changed their treatment approach and there are still families who view the benefit-risk profile of Elevidys positively, Ingram said. About 60% of Elevidys revenue comes from top sites and experts, many of whom are already fully booked out to 12 months, he noted, adding that the company needs to direct much of its attention to other sites with more available capacity.
But the hesitation in the broader DMD community is obvious.
Following the incident, Sarepta “immediately initiated extensive outreach” to doctors and the DMD community to educate them about Elevidys’ data, Murray said.
“Our current focus is on disseminating this information across the wider treating and referring physician landscape, which is a process that takes time,” he said.
Despite the unfortunate death, Elevidys still has “one of the most impressive safety profiles” of AAV-based gene therapies, Ingram said.
The chief executive also argued that the safety signal should be interpreted in the context of Elevidys’ efficacy profile. Two-year MRI results unveiled in January showed that patients treated with the drug had minimal muscle pathology progression. Patients who had originally been treated with placebo, who then crossed over to receive Elevidys, showed statistically significant and clinically meaningful functional benefit across several Duchenne tests compared with an external control group.
However, one analyst raised an investor concern about a worst-case scenario in which Elevidys is pulled from the market. And the appointment of long-time biopharma industry skeptic Vinay Prasad, M.D., as the new leader for the FDA’s Center for Biologics Evaluation and Research does not help with that narrative, the analyst noted.
Ingram wouldn’t comment on Prasad’s appointment.
“What I do remain confident about is that the FDA is going to be the FDA that had been for the last 100 years, which is an organization dedicated to following great science and fulfilling its mission of bringing life-enhancing therapies that are safe and efficacious to patients,” he said.