Jefferies analysts forecast a $1 billion market opportunity for each of Sarepta’s siRNA programs for facioscapulohumeral muscular dystrophy and myotonic dystrophy type 1.
Last year was a difficult one for Sarepta Therapeutics, marked by patient deaths and a drastic pipeline pivot. Things look brighter for the Massachusetts biotech this year, however, with a calendar replete with clinical and regulatory catalysts.
That’s according to analysts at Jefferies, who in a note to investors on Monday pointed to Sarepta’s Arrowhead Pharmaceuticals–partnered siRNA portfolio. This includes SRP-1001 for facioscapulohumeral muscular dystrophy (FSHD) and SRP-1003 for myotonic dystrophy type 1 (DM1), both of which are expected to produce initial Phase I/II data in the first quarter of this year, the firm wrote.
These assets, “could drive a +25 – 50% stock move,” Jefferies said, adding that each program poses a market opportunity of upwards of $1 billion.
Sarepta is also advancing SRP-1005—likewise an siRNA therapy from Arrowhead—for Huntington’s disease. Sarepta filed its clinical trial application earlier this month and expects to launch Phase I studies in the first half of 2026.
Aside from its siRNA pipeline, Jefferies also sees a lot of promise in Sarepta’s commercial portfolio, particularly its phosphorodiamidate morpholino oligomer (PMO) products. On Monday, Sarepta released preliminary fourth-quarter and full-year 2025 earnings figures. In the fourth quarter, the company’s PMO portfolio brought in $259.2 million—an 8% quarter-on-quarter jump, according to Jefferies, which added that this revenue came in above consensus expectations. Full-year 2025 PMO sales hit $965.6 million, a largely flat year-on-year trend.
In November last year, two of these PMOs, Vyondys 53 and Amondys 45, failed their confirmatory study in Duchenne muscular dystrophy (DMD). In the Phase III ESSENCE trial, neither therapy significantly improved motor function versus placebo.
Both Vyondys and Amondys are exon-skippers: They bind to a particular site on dystrophin pre-mRNA, preventing their expression, and resulting in a shorter but functional form of the protein. The former was approved in 2019 and the latter in 2021, both through the FDA’s accelerated pathway.
Despite the confirmatory fail, Sarepta is pushing through with its bid to secure full approval for these therapies. A meeting with the FDA is scheduled in February or March, according to Jefferies. If the company is able to align with the regulator on a path forward, that development could swing Sarepta’s stocks up by around 25%, the analysts estimated.
Last year, Sarepta reported preliminary net product reviews of $1.86 billion. Of these, the DMD gene therapy Elevidys contributed nearly $900 million. Sarepta reported two patient deaths related to Elevidys in 2025—one in March and another in June, both tied to acute liver failure. Fourth quarter Elevidys sales missed analyst expectations—$110 million compared to a conensus estimate of $121 million, according to Jefferies. In July, reeling from the safety scrutiny, the biotech announced a broad pivot to siRNA therapies.
