Sarepta Therapeutics (NASDAQ:SRPT) executives used the company’s fourth-quarter 2025 earnings call to highlight a stronger balance sheet, stable demand for its exon-skipping therapies, and a renewed commercial push for its gene therapy ELEVIDYS following safety-related turbulence in 2025. Management also outlined several near-term clinical and regulatory milestones across its Duchenne muscular dystrophy (DMD) portfolio and its expanding siRNA pipeline, and CEO Doug Ingram announced plans to retire by around the end of 2026.
2025 revenue mix and 2026 revenue outlook
Chief Commercial Officer Patrick Moss said 2025 net product revenue totaled $1.86 billion, consisting of $966 million from Sarepta’s PMO franchise and $899 million from ELEVIDYS. Fourth-quarter PMO net product revenue was $259 million, with $148 million from EXONDYS 51, $34 million from VYONDYS 53, and $77 million from AMONDYS 45.
For 2026, Ingram provided a broad net product revenue range of $1.2 billion to $1.4 billion for approved therapies, noting quarter-to-quarter variability driven by ELEVIDYS’ one-time dosing model and long lead times from enrollment to infusion. He said the company expects first-quarter 2026 revenue to be “about flat to perhaps down 15%” from the prior quarter. Ingram added that, absent new educational initiatives, the company would expect to track toward $1.2 billion, while more immediate impact from those initiatives could push revenue toward $1.4 billion, though he suggested modeling toward the low end given the timing and cycle-time dynamics.
Commercial “reset” for ELEVIDYS after 2025 safety events
Management described 2026 as a “critical reset year” for the ambulatory population, with efforts centered on addressing what Moss called an “information imbalance” about ELEVIDYS’ risk-benefit profile. Ingram said uncertainty stemming from two “tragic” 2025 events has largely cleared, pointing to an updated label, updated precautions and monitoring, and a traditional approval for ambulatory patients ages four and older.
Moss said the company has updated promotional materials to reflect new data, expanded its field footprint beyond treatment centers to include referring physicians and caregivers, and is emphasizing longer-term outcomes, including muscle MRI findings that management said show muscle decline before functional decline is observed. Sarepta described early “green shoots,” including enrollment forms from sites that had not submitted since last summer and increasing participation from sites outside Sarepta’s existing network, though executives repeatedly cautioned that revenue impacts will take time to emerge due to enrollment-to-infusion timelines that can span several months.
Ingram also said the company plans to address disparities in access to information, including increased Spanish-language outreach, noting that patients’ likelihood of receiving ELEVIDYS can vary by socioeconomic factors.
Clinical and regulatory updates: EMBARK, non-ambulatory pathway, and PMOs
Chief Scientific Officer Dr. Louise Rodino-Klapac reviewed positive top-line three-year functional results from Part One of the Phase III EMBARK study, comparing treated patients with a pre-specified propensity-weighted, untreated external control group. She said results showed statistically significant, clinically meaningful, durable efficacy across key motor function measures, including North Star Ambulatory Assessment (NSAA), Time to Rise, and 10 Meter Walk/Run.
- Rodino-Klapac reported a 4.39-point NSAA difference at year three versus the external control group, with a P value of 0.0002.
- She said ELEVIDYS-treated patients showed a 73% slowing of disease progression by Time to Rise and a 70% slowing by 10 Meter Walk/Run versus external controls.
- She said no new safety signals were observed over three years and no treatment-related serious adverse events were reported.
On non-ambulatory patients, Ingram said the FDA approved a sirolimus pretreatment study, which he characterized as an important step toward potentially resuming commercial dosing in non-ambulatory populations if successful. Rodino-Klapac said ENDEAVOR Cohort 8 will enroll approximately 25 U.S. non-ambulatory participants and evaluate dystrophin expression at 12 weeks and whether sirolimus reduces the incidence of acute liver injury. She said Sarepta initiated the cohort in late 2025, is currently screening patients, and expects to share findings by the end of 2026. In Q&A, she added that restarting the ENVISION trial in the U.S. is expected to be informed by Cohort 8 data.
For Sarepta’s exon-skipping therapies AMONDYS 45 and VYONDYS 53, Ingram said ESSENCE results support the risk-benefit profile and that a meeting with the FDA is scheduled later in the first quarter to discuss potential transition to traditional approval. Rodino-Klapac said the company has submitted a briefing book for that meeting. Ingram emphasized the PMO franchise’s long-standing real-world evidence base and high compliance rates, while Moss said PMO demand has declined modestly as patients choose ELEVIDYS.
Financial results, margin impacts, and Roche collaboration items
CFO Ryan Wong said total 2025 revenue was $2.2 billion, up 16% year over year, including $334 million in collaboration, contract manufacturing, and royalty revenue from the Roche partnership.
Wong detailed significant 2025 cost-of-sales impacts tied to manufacturing recalibration. Fourth-quarter cost of sales was $399 million, including a $193 million charge from raw material inventory and purchase commitment adjustments (comprised of $165 million in non-cash reserves and $28 million in cancellation fees). Full-year cost of sales totaled $840 million, with nearly half reflecting failed batches, reserves, and other period charges; excluding those charges, Wong said unit sales-driven margins were in the low 80% range for the year. For 2026, he said production volumes will be significantly lower, and the company expects unit-volume margins in the high 70% range.
Wong reaffirmed Sarepta’s 2026 non-GAAP operating expense outlook of $800 million to $900 million. He also described progress addressing 2027 debt through a second debt exchange that refinanced $291 million of 2027 notes into 2030, leaving $159 million remaining. Sarepta ended 2025 with $954 million in cash and investments, up $89 million in the fourth quarter, and Wong said the base business generated more than $330 million of positive cash flow in 2025 excluding Arrowhead payments.
Looking to 2026 collaboration-related items, Wong said ELEVIDYS has now launched in Japan and Sarepta expects to record a $40 million milestone payment from Roche in the first quarter upon first commercial sale. He also said Sarepta anticipates recognizing $325 million of non-cash collaboration revenue tied to Roche declining an option for a specific program, and projected total 2026 collaboration, contract manufacturing, and royalty revenue of $450 million to $550 million.
Pipeline milestones and CEO succession planning
Rodino-Klapac said Sarepta plans to announce preliminary proof-of-concept data for its DM1 and FSHD siRNA programs at the end of the first quarter, with an emphasis on safety and pharmacokinetics (including serum and muscle PK) and preliminary pharmacodynamics where available. In Q&A, she said early PD readouts will include DMPK knockdown for DM1 and DUX4-targeted gene correction for FSHD, while DM1 splicing panel data (CASI-22) is expected in the second half of the year.
She also said Sarepta has initiated its Huntington’s disease trial (SRP-1005) in New Zealand after Medsafe accepted the clinical trial application, with first dosing expected in the first half of 2026.
Ingram announced he has informed Sarepta’s board he intends to retire as CEO by around the end of 2026, citing family commitments, including that two immediate family members have been diagnosed with myotonic dystrophy (DM1). He said the board has initiated a comprehensive successor search with both internal and external candidates.
About Sarepta Therapeutics (NASDAQ:SRPT)
Sarepta Therapeutics, Inc is a biopharmaceutical company focused on the discovery and development of precision genetic medicines for rare neuromuscular diseases. Headquartered in Cambridge, Massachusetts, Sarepta’s core expertise lies in designing RNA-targeted therapies and gene therapies that address underlying genetic mutations. The company’s mission is to transform the treatment paradigm for patients with Duchenne muscular dystrophy (DMD) and related disorders through innovative modalities.
Sarepta’s commercial products include several exon-skipping therapies approved by the U.S.
