One To Watch

Sarepta Therapeutics

A Cambridge, Massachusetts-based commercial-stage biotechnology company shifting its center of gravity from gene therapy toward siRNA in rare neuromuscular disease, with four FDA-approved products and a restructured pipeline under new chief executive Michael Severino.

Company Overview

Sarepta describes itself as focused on RNA-targeted therapeutics, siRNA knockdown therapies, gene therapy and other genetic therapeutic modalities for rare diseases. The company's commercial base rests on three phosphorodiamidate morpholino oligomer (PMO) exon-skipping drugs for Duchenne muscular dystrophy and ELEVIDYS, its AAV-based gene therapy.

Shares trade on the Nasdaq Global Select Market under the ticker SRPT.

Headquarters and Global Presence

Sarepta's corporate headquarters is at 215 First Street, Cambridge, Massachusetts, with additional facilities in Andover, Burlington and Bedford, Massachusetts, Columbus, Ohio and Durham, North Carolina.

As of December 31, 2025 the company employed 835 people globally, following the elimination of approximately 500 roles, roughly 36% of the workforce, in the July 2025 restructuring.

Gene therapy manufacturing is conducted through contract manufacturing organizations including Aldevron and Catalent; Sarepta has no internal GMP manufacturing capability for commercial or clinical supply.

Founding and History

The company was originally incorporated in Oregon on July 22, 1980 and reincorporated in Delaware on June 6, 2013. It operated as AVI BioPharma before changing its corporate name to Sarepta Therapeutics and its Nasdaq ticker to SRPT effective July 12, 2012, following shareholder approval.

The first of its PMO exon-skipping drugs, eteplirsen (EXONDYS 51), received FDA accelerated approval in 2016, establishing Sarepta as the leader in Duchenne oligonucleotide therapy before the June 2023 accelerated approval of ELEVIDYS extended the franchise into gene therapy.

Therapy Areas and Focus

Sarepta's franchise is anchored in Duchenne muscular dystrophy, a progressive X-linked disease with incidence commonly estimated at one in 3,500 to 5,000 male births and no curative treatment.

Beyond Duchenne, the restructured pipeline targets facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy type 1 (DM1), a disease with no approved disease-modifying therapy, spinocerebellar ataxia, idiopathic pulmonary fibrosis and Huntington's disease through the Arrowhead collaboration.

That reflects a deliberate concentration on the genetics of muscle and neurodegenerative disease rather than a broad rare-disease footprint.

Technology Platforms and Modalities

Sarepta operates across three modalities. Its original PMO chemistry enables exon-skipping in the dystrophin pre-mRNA, restoring a truncated but partially functional dystrophin protein in patients whose mutations are amenable to skipping of specific exons.

ELEVIDYS uses an AAVrh.74 vector to deliver a shortened microdystrophin gene construct, aiming for a more durable effect with a single infusion. The siRNA platform, licensed through the Arrowhead collaboration and now the company's declared strategic priority, uses an alpha-v beta-6 integrin-targeted delivery approach to knock down disease-causing transcripts in skeletal muscle.

The mechanism has potential applicability well beyond Duchenne.

Key Pipeline and Programs

ELEVIDYS (delandistrogene moxeparvovec-rokl) is an AAVrh.74-based microdystrophin gene therapy with traditional FDA approval, as of June 2024, for ambulatory Duchenne patients aged four and older. Its non-ambulatory indication was removed in November 2025 following two fatal cases of acute liver failure in that population.

Three-year EMBARK data reported in January 2026 showed treated ambulatory patients maintained motor function above baseline while an external control group declined, with a reported 73% slowing of disease progression on the time-to-rise measure. These are company-reported results measured against an external comparator rather than a randomized control arm.

SRP-9003 (bidridistrogene xeboparvovec) is an AAVrh.74 gene therapy targeting LGMD2E (beta-sarcoglycanopathy), designed to deliver a beta-sarcoglycan gene and restore the dystrophin-associated protein complex. The Phase 3 EMERGENE trial completed enrollment in December 2024 and reported safety and expression results in October 2025.

The program remains on FDA clinical hold, placed July 2025 after a death in the Phase 1 SRP-9004 LGMD trial; the FDA has said it requires sirolimus immunosuppression data before accepting a BLA.

SRP-1001 and SRP-1003 are siRNA candidates targeting DUX4 in FSHD1 and DMPK in DM1, respectively, using the alpha-v beta-6 integrin-targeted delivery system licensed from Arrowhead. Both are in Phase 1/2 ascending-dose studies.

First clinical data reported March 25, 2026 showed dose-dependent muscle exposure, single-dose target knockdown and favorable tolerability. Further data are expected in the second half of 2026, with pivotal studies indicated for 2027.

Recent Developments

The defining events of the past 12 months were the 2025 safety reports. Two non-ambulatory teenage Duchenne patients who had received ELEVIDYS died of acute liver failure, reported in March and June 2025, and a patient in the Phase 1 trial of the LGMD candidate SRP-9004 died of liver failure 80 days after dosing.

Sarepta temporarily halted all US ELEVIDYS shipments in July 2025 at the FDA's request, the non-ambulatory indication was later removed and a boxed warning for acute liver injury and acute liver failure added. The FDA also revoked the platform technology designation for the AAVrh74 vector and placed a clinical hold across the LGMD gene therapy programs.

In parallel, the November 2025 ESSENCE confirmatory trial for AMONDYS 45 and VYONDYS 53 failed to meet its primary endpoint; the FDA nevertheless accepted supplemental NDAs for filing in June 2026 with a PDUFA date of February 28, 2027. Michael Severino, M.D., was appointed chief executive effective July 28, 2026, succeeding Doug Ingram, who had led the company since June 2017.

Key Personnel

Michael Severino, M.D., became Chief Executive Officer on July 28, 2026 and joined the board. He succeeded Doug Ingram, who is retiring and remains with the company in an advisory capacity through the end of 2026.

Severino was previously chief executive of Tessera Therapeutics and a CEO-Partner at Flagship Pioneering, and before that vice chairman and president at AbbVie, where he oversaw approvals including Rinvoq, Skyrizi and Venclexta. He holds an M.D. from Johns Hopkins University and trained at Massachusetts General Hospital.

Ian Estepan serves as President and Chief Operating Officer and Louise Rodino-Klapac as President of Research and Development and Technical Operations. Ryan H. Wong serves as Executive Vice President and Chief Financial Officer, identified in SEC filings as the company's principal financial and accounting officer.

Strategic Partnerships

Sarepta's most significant current partnership is with Arrowhead Pharmaceuticals, under an exclusive global license and collaboration agreement that became effective February 7, 2025.

Under that deal Sarepta paid Arrowhead $500 million upfront and $325 million through a purchase of Arrowhead common stock at $27.25 per share, plus $250 million payable in annual installments of $50 million over five years, securing rights across the FSHD, DM1, ataxia, IPF and Huntington siRNA programs.

Sarepta also holds a collaboration with F. Hoffmann-La Roche for ex-US ELEVIDYS rights; Roche's Japanese affiliate Chugai launched ELEVIDYS in Japan in February 2026, though the EMA issued a negative opinion in July 2025.

In February 2026 Roche declined to exercise an option for certain program rights, triggering $325 million of collaboration revenue recognition in Sarepta's first quarter 2026 results.

FAQ Section

The 2025 safety reports forced the issue. Two non-ambulatory Duchenne patients who had received ELEVIDYS died of acute liver failure, and a third patient died in the Phase 1 trial of the LGMD candidate SRP-9004, which uses the same AAVrh74 vector.

A boxed warning followed, the non-ambulatory indication was removed, and the FDA revoked the AAVrh74 platform technology designation. The July 2025 restructuring, which cut approximately 500 roles and targeted roughly $400 million in annual savings, explicitly reprioritized the pipeline around the siRNA platform.

Getting siRNA into skeletal muscle at therapeutic levels has historically been the central challenge of RNA interference in neuromuscular disease, because most systemic siRNA delivery platforms are optimized for the liver.

The alpha-v beta-6 integrin receptor is expressed on muscle cells, and Arrowhead's targeted delivery approach is designed to direct the siRNA payload specifically into skeletal muscle.

The March 2026 FSHD and DM1 data showing dose-dependent muscle exposure and single-dose target knockdown are early but meaningful evidence that the delivery mechanism is working as designed, which is what makes the platform commercially interesting beyond any single indication.

The PMO drugs, eteplirsen, golodirsen and casimersen, each address a specific exon mutation subset, meaning each product reaches only the fraction of Duchenne patients whose mutation is amenable to skipping of exon 51, 53 or 45, respectively.

Gene therapy with ELEVIDYS delivers a microdystrophin construct that works regardless of the underlying exon mutation, broadening eligible patient numbers substantially.

The siRNA programs operate by suppressing pathological transcripts rather than restoring a functional protein, a mechanism applicable to diseases like DM1 and FSHD where the target is a toxic gain-of-function RNA rather than a protein-coding loss.

ELEVIDYS holds traditional FDA approval for ambulatory Duchenne patients aged four and older, with shipments to that population resumed July 31, 2025. The non-ambulatory indication was formally removed in November 2025, and the label now carries a boxed warning for acute liver injury and acute liver failure including fatal outcomes.

ELEVIDYS net product revenue was $102.0 million in the first quarter of 2026, down 73% from $375.0 million a year earlier.

Outside the US, Chugai launched the product in Japan in February 2026, but the EMA issued a negative opinion in July 2025; Roche has since initiated a new placebo-controlled Phase 3 trial in approximately 100 early ambulatory Duchenne patients to support EMA resubmission.

The Arrowhead collaboration extends Sarepta's reach into FSHD, myotonic dystrophy type 1, spinocerebellar ataxia, idiopathic pulmonary fibrosis and Huntington's disease, all accessed through the same siRNA delivery platform. DM1 is particularly notable as a large unmet need with no approved disease-modifying therapy.

The gene therapy pipeline also retains SRP-9003 for LGMD2E (beta-sarcoglycanopathy), though this program remains on FDA clinical hold pending sirolimus immunosuppression data. The overall shape is that of a muscle and neurological RNA company rather than a diversified rare-disease business.

Sarepta is genuinely commercial, with four approved products and $330.5 million in net product revenue in Q1 2026, though ELEVIDYS revenues have fallen sharply from their peak in 2024 and 2025. The company guided for full-year 2026 revenues of $1.2 billion to $1.4 billion and held $748.3 million in cash and investments at March 31, 2026.

The siRNA programs SRP-1001 and SRP-1003 are at Phase 1/2 with pivotal studies targeted for 2027, making the second half of 2026 data updates the critical near-term read on whether the new platform direction is viable.

The February 28, 2027 PDUFA date for the AMONDYS 45 and VYONDYS 53 supplemental NDAs is the next major regulatory event for the existing franchise.

Key watchpoints include:

Second-half 2026 siRNA data updates for SRP-1001 (FSHD) and SRP-1003 (DM1): these will determine whether the new platform holds up beyond a single-dose signal and whether pivotal designs are viable for 2027.
FDA decision on the AMONDYS 45 and VYONDYS 53 supplemental NDAs (PDUFA February 28, 2027): failure to convert these accelerated approvals to traditional approval would remove two revenue-generating products.
Resolution of the SRP-9003 clinical hold: the FDA requires sirolimus immunosuppression data before accepting a BLA, and the timeline depends on Cohort 8 of Study 9001-103.
ELEVIDYS non-ambulatory pathway: any resumption of commercial dosing in that population depends on FDA acceptance that sirolimus changes the risk/benefit calculation.
Shareholder litigation: a securities class action covering the period June 22, 2023 to November 3, 2025 is proceeding in the District of Massachusetts, with unproven allegations of misleading ELEVIDYS safety and efficacy disclosures.
Leadership transition: new chief executive Michael Severino's strategy for the rebuild, particularly capital allocation between gene therapy and siRNA, will be closely watched.

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