If one word described Sarepta’s 2025, “darkest hour” would fit perfectly.

At the start of the year, Sarepta was still a Wall Street favorite. By mid-2024, its market cap hit an all-time high, with investors pinning huge hopes on Elevidys, projecting billions in sales.

Yet misfortune arrived quietly in the spring. Two Elevidys‑related deaths in 2025 sent the stock spiraling downward. Soon after, a third death was reported, linked to an investigational limb-girdle muscular dystrophy gene therapy using the same AAV vector as Elevidys.

From start to finish, Sarepta’s stock plummeted more than 80% to a decade low, wiping out roughly $13 billion from its 2024 peak. Elevidys, once hailed as a “gene therapy miracle,” quickly became a toxic asset.

In June 2025, Sarepta suspended shipments of Elevidys to non-ambulatory patients (older and more severely affected). The FDA simultaneously tightened regulations and updated the therapy’s label with strengthened safety warnings.

Elevidys sales also fell short of expectations.The therapy generated $375 million in Q1 2025, dropping to $282 million in Q2. For the full year, net sales reached $898.7 million, but Q4 revenue of just $110 million missed the consensus estimate of $120.5 million. The company blamed a severe flu season and six infusion delays.

Sarepta’s total revenue rose 16% year-over-year to $2.2 billion, with exon-skipping PMO therapies contributing $965.6 million.

Beneath the headline growth, however, lay a grim reality: a Q4 loss of $3.58 per share, far below estimates, and ongoing annual losses. Although the firm strengthened its finances via debt restructuring, ending the year with nearly $1 billion in cash and projecting profitability in 2026, investor confidence had already eroded.

Weakness in core products and an over-reliant pipeline were major factors. Sarepta concentrated too heavily in DMD; beyond Elevidys and PMO therapies, it lacked competitive pipeline assets. Its bet on siRNA had yet to deliver growth, and multiple R&D programs were halted in 2025.

The nightmare was far from over.

In November 2025, Sarepta suffered arguably the heaviest blow in its history. Vyondys 53 and Amondys 45 — two PMO therapies approved via accelerated pathways in 2019 and 2021, respectively — failed to meet their primary endpoint in the pivotal confirmatory ESSENCE trial.

Data showed a minimal 0.05 steps/second improvement in motor function, which was not statistically significant. Despite years on the market and billions in revenue, the drugs had never proven they could truly alter DMD disease progression in a rigorous placebo-controlled trial.

After the announcement, Sarepta’s stock crashed 37% in after-hours trading. For a company focused on DMD for nearly a decade, two of its three flagship product lines had collapsed in late-stage trials.

In response, Sarepta partially blamed COVID-19, claiming the pandemic “impacted study participants and trial outcomes.” The company also announced it would continue pursuing full approval for Vyondys 53 and Amondys 45, citing “encouraging trends” and “substantial real-world evidence” supporting their value.

Optimism for this path remains low.

In 2025, the FDA revised regulatory policies to raise evidence standards for rare disease therapies and reform the accelerated approval pathway, reducing controversial approvals. This dealt a heavy blow to Sarepta, which had risen on Exondys 51 and Elevidys. The FDA also maintained strict oversight of Elevidys, requiring long-term safety data and increasing compliance and R&D pressure.

One analyst noted: “Given the turmoil of the past year, news of his [Ingram’s] planned retirement may not come as a surprise.”

Before 2016, Sarepta suffered consistent losses and faced a cash crunch. Back then, DMD patients relied on steroids to slow disease progression.

Notably, Sarepta’s Exondys 51 won FDA accelerated approval that year, becoming the world’s first DMD drug. It targeted the 13% of patients with exon 51 deletions, using exon skipping to produce functional dystrophin.

The approval sparked fierce debate: the clinical trial was extremely small (only 12 patients in the main study, no placebo control), with results only confirming increased protein expression — not improved motor function or survival. A majority of the FDA advisory committee voted against approval, but the FDA ultimately approved it due to the unmet medical need in DMD.

After Doug Ingram took office in 2017, he set a core strategy: “Focus on DMD and build a full pipeline,” accelerating PMO therapy development. Vyondys 53 (2019) and Amondys 45 (2021) gained approval in succession.

All three drugs shared the same logic: using antisense oligonucleotide technology to skip specific exons in the dystrophin pre-mRNA, producing a shorter but functional protein. All were approved via accelerated pathways, based primarily on biomarkers rather than clinical endpoints.

In June 2023, Sarepta made history again. Despite mixed and limited data, the FDA approved Elevidys — the world’s first DMD gene therapy, for ambulatory children aged 4 to 5.

This success catapulted Sarepta’s industry status, with its market cap briefly surpassing $13 billion.

Sarepta also partnered with Novartis to boost Elevidys manufacturing and global commercialization. It struck a major deal with Arrowhead Pharmaceuticals: $500 million upfront plus $325 million in equity investment to bet on its RNAi platform. The collaboration covered myotonic dystrophy type 1, facioscapulohumeral muscular dystrophy, and other areas, with potential milestone payments reaching $10 billion.

Ingram’s vision was to transform Sarepta from a DMD-focused firm into a comprehensive leader in neuromuscular rare diseases. “We set ambitious goals, chief among them to reduce the disease burden and extend the lives of boys and young men with DMD.”

Yet between vision and reality stood the year 2025.

When Sarepta released Q4 results, it tried to strike an optimistic tone: full-year revenue rose 16%, PMO therapies covered roughly 30% of DMD patients, and “strong demand-driven performance” demonstrated durability.

Executives likely hoped new three-year Elevidys data would turn the tide. But William Blair said the data would be only incrementally positive, unlikely to meaningfully boost prescriptions or adoption in the near term.

Sarepta’s president of R&D and technical operations defended the therapy: “The data speak for themselves. We saw a greater than four-point difference in NSAA scores. The effect increases over time, and I believe that is what truly matters.”

Nevertheless, the stock has dropped another 12% since the announcement. Investors posed a simple question: If the data are so strong, why aren’t sales growing?

Sarepta Chief Commercial Officer Patrick Moss admitted on the call that “awareness was insufficient.” Physicians and families remained hesitant about gene therapy, partly due to the 2025 deaths. Even after the FDA cleared Elevidys for ambulatory patients, provider concerns have not faded easily.

A bigger challenge is competition.

In October 2025, Novartis acquired Avidity Biosciences for approximately $12 billion. Avidity’s exon 44-skipping drug del-zota is expected to be filed for BLA in Q1 2026, with one-year data showing “reversal of disease progression.” Analysts predict a smooth launch given the lack of approved exon 44 therapies.

Capricor Therapeutics’ cell therapy deramiocel received a complete response letter from the FDA in July 2025, then demonstrated positive Phase III results in December and is now under review. REGENXBIO plans to report top-line data for its gene therapy RGX-202 — a potential Elevidys rival — in Q2, with a BLA filing targeted for mid-2026. Solid’s gene therapy SGT-003 is in Phase I/II.

Another potential contender comes from Dyne Therapeutics: zeleciment rostudirsen (z‑rostudirsen) for DMD patients eligible for exon 51 skipping. In Phase I/II data released last December, Stifel analysts called it the “best-ever” functional improvement for a DMD exon-skipping drug. A Phase III trial is set to begin in Q2, with Dyne pursuing accelerated approval.

A harsh reality confronts Sarepta: AAV can only be administered once. Patients who receive Elevidys will not be eligible for RGX-202 or SGT-003.

Given patient frustration and a damaged brand, the head of rare disease and gene therapy consultancy Acadia Strategy Partners stated the biotech is not even an attractive acquisition target for large pharma. “The story has gone on too long. Their best days are behind them.”

For 2026, Sarepta expects Elevidys sales to be flat or down 15%. It plans to expand its sales force, launch marketing campaigns, and improve patient communication. But analysts noted even these efforts would not take effect until the second half.

Still, Sarepta holds cards: its PMO portfolio generates steady cash flow; the siRNA therapy SRP-1005 for Huntington’s disease is expected to enter Phase I in H1 2026; and its Arrowhead siRNA platform advances in DM, FSHD, and other areas. As of the end of 2025, the company held nearly $1 billion in cash and investments.

On its earnings call, Sarepta issued conservative 2026 guidance: total product revenue of $1.2–1.4 billion, down from $1.86 billion in 2025.

Following the CEO’s departure, Sarepta has launched a search for a successor, considering both internal and external candidates. COO Ian Estepan is viewed as a potential pick. Whoever takes over will face a complex landscape: regulatory uncertainty for core products, a safety trust crisis for gene therapy, a flood of competitors, and wavering patient confidence.

In 2026, as new gene therapies reach the FDA and safer options may emerge, the history of DMD treatment will turn a new page. Whether Sarepta can claim a place in the new narrative depends on its next leader’s wisdom and courage — and perhaps a touch of fate.