The abrupt suspension of Sarepta Therapeutics’ Elevidys gene therapy in July 2025 following multiple patient deaths marked a defining moment for the gene therapy sector. The FDA's intervention, platform revocation, and heightened safety scrutiny triggered cascading effects across the industry, from developers and CDMOs to investors and regulators. Yet while the crisis exposed critical flaws in communication, oversight, and risk management, it also presented an opportunity for reflection and recalibration. This article examines what went wrong, how the sector is responding, and what steps must be taken to rebuild trust. With more disciplined oversight, transparent disclosure, and risk-aware innovation, gene therapy can still fulfill its transformational promise.
Introduction: A Shock to the System
In July 2025, the gene therapy sector was rocked by a crisis that unfolded with stunning speed. Sarepta Therapeutics, once viewed as a leader in genetic medicines for rare neuromuscular diseases, abruptly suspended shipments of its flagship gene therapy Elevidys following the deaths of multiple trial participants. What began as internal concern over adverse events quickly escalated into a full-fledged regulatory intervention, as the U.S. Food and Drug Administration (FDA) requested the halt of commercial distribution and placed multiple clinical trials on hold. The company’s initial resistance to the FDA’s request, followed by a reluctant reversal amid public and investor backlash, only intensified scrutiny.
This incident has since been framed as a turning point for gene therapy. Some have questioned whether the sector’s momentum can survive such a public failure, speculating that this may represent the beginning of a broader unraveling of confidence in adeno-associated virus (AAV)-based therapies. However, writing off gene therapy altogether in this moment would be premature and ultimately unhelpful. The Sarepta case is not evidence of the field’s collapse but rather a stark reminder of the risks inherent in pushing scientific innovation into clinical practice without adequate transparency, communication, or nuance.
Here, we explore the circumstances that led to the Sarepta–FDA standoff, the implications for developers, contract development and manufacturing organizations (CDMOs), investors, and regulators, and what it will take for the sector to regain trust. The path forward will demand a more disciplined, transparent, and risk-aware approach. But that path still exists. The promise of gene therapy promise remains, but its future now depends on whether the field can adapt to a new era of accountability.
The Sarepta–FDA Showdown
The sequence of events that unfolded in mid-2025 around Sarepta Therapeutics and its gene therapy Elevidys marked one of the most significant regulatory confrontations the gene therapy sector has seen to date. Elevidys, designed to treat Duchenne muscular dystrophy (DMD) using an AAVrh74 vector, had been granted accelerated approval for ambulatory patients in 2023, with expectations for broader use pending further data. But in July 2025, the FDA initiated a safety review following the deaths of three patients — two adolescents with DMD and one adult with limb-girdle muscular dystrophy (LGMD) — who had received the therapy under either commercial access or investigational protocols.1,2
In response to these deaths, the FDA requested that Sarepta immediately suspend all U.S. shipments of Elevidys and halt ongoing clinical trials using the same vector. Rather than complying, Sarepta issued a public rebuttal asserting that there were no new safety signals warranting such action in the ambulatory DMD population. This defiance was met with growing concern from stakeholders, particularly as a previously undisclosed fourth death — an eight-year-old patient in Brazil — came to light during this period.3,4 Although the FDA later determined that the Brazilian case was not causally linked to the therapy, the company's initial decision not to disclose it compounded reputational damage.
The regulatory pressure did not stop with a shipment hold. The FDA revoked Sarepta’s platform technology designation for AAVrh74, signaling that future submissions would require individual data packages rather than benefiting from streamlined review under the prior platform umbrella.1 The agency also proposed adding black box warnings to Elevidys labeling, further highlighting safety concerns.
On July 28, the FDA permitted Sarepta to resume Elevidys shipments, but only for ambulatory DMD patients, where the benefit–risk profile appeared more favorable.3 The use of Elevidys in non-ambulatory patients remains suspended as regulators and the company evaluate the need for stricter eligibility criteria, additional safety monitoring, and potential label changes.
In parallel with the regulatory crisis, Sarepta initiated a sweeping corporate restructuring. Roughly 500 employees (approximately 36% of the workforce) were laid off in July, and the company signaled a strategic shift away from systemic gene therapy toward its RNA-based and LGMD programs.5,6 While the official rationale focused on aligning resources with high-impact opportunities, many viewed the move as a direct consequence of the FDA’s actions and an admission of the damage done.
The fallout extended beyond operations. Sarepta’s inconsistent communication — delayed acknowledgment of patient deaths, optimistic public statements contradicting regulatory actions, and opaque clinical disclosures — undermined investor and stakeholder trust. As scrutiny intensified, the company’s valuation collapsed, and its once-promising leadership position in gene therapy became a cautionary tale for the sector.7,8
Sector-Wide Fallout: Who Felt the Shockwaves
The crisis was not contained to one company or one therapy. Its ripple effects were felt across the gene therapy ecosystem, triggering renewed skepticism, regulatory recalibration, and market repricing. Developers, CDMOs, regulators, and investors alike were forced to reevaluate long-held assumptions about the safety, scalability, and oversight of gene therapies, particularly those involving systemic AAV administration.
Gene Therapy Developers
For developers, the most immediate impact was reputational. The deaths associated with Elevidys — though still under investigation — cast a long shadow over the entire field. A sense of “guilt by association” emerged, with both AAV and non-AAV gene therapy programs facing heightened scrutiny from institutional review boards, regulators, and potential partners. Even companies with entirely distinct vectors or delivery modalities found themselves fielding questions about risk mitigation and adverse event transparency.9
This environment has intensified the focus on foundational design choices. Vector selection, dosing strategies, and inclusion criteria are under the microscope, with particular attention paid to patient comorbidities, especially hepatic function. Trial protocols that had previously passed through review without challenge are now being reconsidered or delayed, as sponsors and regulators take a more cautious approach to systemic gene delivery in pediatric or fragile populations.
The revocation of Sarepta’s platform designation also sent a broader message: regulators may no longer accept that one successful filing using a particular vector ensures a smooth path for follow-on programs. Developers who have relied on platform designations to accelerate pipelines are now navigating a landscape where each therapy may need to stand entirely on its own merits.1
Contract Development and Manufacturing Organizations
CDMOs, especially those with business models built around AAV manufacturing, are also feeling the effects. In the near term, some projects may be delayed or deprioritized as sponsors revisit trial plans or retool product designs in light of emerging safety concerns. While overall demand for viral vector manufacturing remains strong, uncertainty surrounding the regulatory posture toward AAV-based systemic delivery could slow investment in certain capabilities.10
At the same time, the moment presents an opportunity for CDMOs to evolve. Developers are seeking deeper scientific partnerships that offer not only technical execution but also input on patient stratification, dose optimization, and long-term safety planning. CDMOs able to support these strategic needs, particularly through integrated services that blend CMC expertise with clinical pharmacology and pharmacovigilance, may emerge stronger as the sector resets its expectations.11
There is also growing interest in next-generation vector systems that offer enhanced targeting, reduced immunogenicity, or non-viral delivery options. CDMOs with experience in these emerging technologies are likely to see increased demand as developers seek to de-risk future programs.
Regulators
The Sarepta case has reinforced the FDA’s shift away from broad platform assumptions and toward more individualized, product-specific assessments. While platform designations were once seen as a way to streamline oversight and reward technological consistency, the events surrounding Elevidys illustrate the limitations of that model. Even therapies using the same vector and manufacturing process may perform very differently depending on patient population, delivery route, or coexisting health conditions.1
In addition to reasserting case-by-case review, the agency is placing more emphasis on long-term safety monitoring and international data sharing. As gene therapies often involve a single administration with lifelong implications, regulators are now pressing for more robust post-marketing surveillance, greater transparency around global adverse event reporting, and potentially new guidance documents for vulnerable subpopulations, such as pediatric patients with neuromuscular diseases.12
Investors
Perhaps no group reacted more immediately than investors. The Sarepta news triggered a sharp decline in the company’s share price, but it also set off a broader revaluation of risk across the gene therapy space. Investors began to pull back from smaller or single-asset companies in favor of those with broader pipelines, adjacent platforms like CRISPR or small interfering RNA (siRNA), or more established safety profiles.7
Risk appetite has shifted decisively. Where once the narrative centered on upside potential and pipeline velocity, the focus has turned to clinical execution, disclosure practices, and worst-case scenarios. This repricing reflects not just the tragedy of individual outcomes, but a recalibration toward the practical challenges of delivering high-dose, systemically administered gene therapies in real-world settings.
While this market correction is painful in the short term, it may ultimately result in a healthier funding environment that prioritizes scientific rigor, operational excellence, and long-term viability over hype cycles.
Lessons Learned: A Hard Reset, Not a Death Sentence
The Sarepta crisis has inevitably drawn comparisons to the 1999 death of Jesse Gelsinger, the first widely publicized fatality in a gene therapy trial. That event prompted a near-total shutdown of gene therapy research, a collapse in funding, and a decade-long erosion of public trust. What’s striking in contrast is that the response to the Elevidys tragedy — while swift and serious — has been more measured. Trials have been paused, platform designations revoked, and safety scrutiny intensified, but the sector has not recoiled in fear or shut down altogether. This reflects how far the field has come: both in its technical sophistication and its institutional maturity. Today’s developers, regulators, and investors are responding not with abandonment, but with accountability — recognizing that while the science holds promise, its execution must catch up.
The fallout from this crisis has offered the gene therapy field a sobering set of lessons. While the scientific potential of gene transfer technologies remains substantial, the events of 2025 exposed the fragility of public trust and the structural vulnerabilities that can emerge when optimism outpaces oversight. This was not the failure of a single molecule nor an indictment of the entire modality. It was a convergence of misjudged risk, communication failures, and overreliance on regulatory shortcuts — each of which canbe corrected.
Underappreciated Risk
For much of the past decade, gene therapy has advanced under the banner of unprecedented innovation. Rapid approvals, high-profile investments, and transformative outcomes for some patients contributed to a narrative that treated success as inevitable. Yet biology remains stubbornly complex, especially in systemically delivered, high-dose AAV therapies. The liver has long been understood as a potential vulnerability in these approaches, but preclinical toxicity signals, often viewed as manageable or species-specific, now appear in a harsher light.
The deaths under investigation in the Elevidys program, particularly those linked to acute liver failure, underscore that enthusiasm alone is not a substitute for fully quantified risk. The ability to prevent such events will depend not just on better science, but on a more disciplined process for recognizing and acting on early warning signs, even when they emerge in small or imperfect data sets.1,9
Transparency Is Non-Negotiable
One of the most damaging aspects of the Sarepta episode was not just the occurrence of adverse events, but the company’s handling of that information. The delayed disclosure of a third patient death and the omission of a fourth case in Brazil created the impression that material information was being withheld, even if the underlying cause remained under investigation.3,4 In a field where patient safety is paramount and regulatory scrutiny is constant, such lapses are not just tactical errors; they are existential threats to credibility.
Developers must treat communication as a core part of their risk management strategy. This means having predefined protocols for evaluating and disclosing serious adverse events, including mechanisms for flagging uncertain or unconfirmed cases to regulators, trial sites, and the public. The instinct to protect shareholder confidence or preserve narrative continuity must never take precedence over clinical transparency.
Platforms Are Not Immunity Shields
Platform designations have often been celebrated for streamlining development, particularly for rare disease programs where repeating full safety evaluations for each new vector application can slow progress and raise costs. However, the Sarepta case has shown that platform status is conditional, not permanent, and that it does not insulate developers from scrutiny when clinical outcomes diverge from expectations.
The FDA’s decision to revoke Sarepta’s AAVrh74 platform designation was a reminder that such privileges must be earned continuously rather than presumed indefinitely.1 The industry’s tendency to treat AAV platforms as modular and interchangeable — plug-and-play systems where only the gene of interest changes — has led to blind spots in evaluating how vector performance varies by context. Tissue tropism, immune response, and toxicity profiles can shift dramatically depending on patient characteristics and administration protocols. Platform thinking can aid development, but it must never override rigorous, case-specific evaluation — especially when each rare disease, and each patient living with it, presents unique risks, vulnerabilities, and lived experiences.
Precision Medicine Needs Precision Oversight
The gene therapy field has long positioned itself as the vanguard of precision medicine. But true precision requires more than targeted genetic payloads; it demands a granular understanding of patient heterogeneity and the capacity to tailor risk mitigation accordingly. The outcomes observed in the Elevidys program illustrate this clearly: ambulatory patients appeared to tolerate treatment more safely than non-ambulatory ones, and age, liver health, and comorbid conditions likely played meaningful roles in determining outcomes.7,10
Going forward, developers must build risk stratification into every phase of their programs, from trial design through commercial rollout. This includes not only selecting appropriate inclusion criteria but also segmenting by delivery route, dosing thresholds, and immunologic profile. Precision medicine cannot succeed with one-size-fits-all safety models. It demands a layered approach that sees individual risk not as a confounding variable but as a design feature to be accounted for from the outset.
Taken together, these lessons do not foreclose the future of gene therapy. Rather, they establish the terms under which that future can be realized responsibly. The Sarepta crisis may well be remembered as a turning point — not because it ended an era, but because it finally demanded a higher standard.
Amid discussions of platforms, vectors, and regulatory designations, it is vital to remember what’s truly at stake: the lives of patients and families who entrust their futures to experimental science. For the individuals who died after receiving Elevidys — and for their loved ones — the promise of innovation became a devastating loss. Rare disease communities often see clinical trials not just as research, but as hope. That hope must never be taken lightly. Every gene therapy candidate represents more than a molecule; it represents a person, a story, a risk borne with courage. The field’s future depends on treating that trust with the reverence it deserves.
The Path Forward: How to Build Resilience and Restore Trust
If the Sarepta crisis served as a stress test for the gene therapy ecosystem, the way forward must be defined by more than retrospective analysis. Rebuilding confidence will require intentional recalibration by all stakeholders: not a retreat from innovation, but a re-anchoring in responsibility. The urgency of the work these therapies aim to address has not diminished. What must change is how that work is executed, communicated, and governed.
For Developers
The first step for gene therapy developers is to reassess assumptions that may have calcified during years of sector-wide momentum. Vector safety, particularly for high-dose, systemically delivered therapies, can no longer be treated as a solved problem. New attention must be given to capsid tropism, transgene expression control, and immunogenicity, especially in light of emerging clinical data that highlight context-dependent toxicity profiles.9,10
Developers must also rethink how they define and apply eligibility criteria. Rather than defaulting to broad enrollment to capture marketable populations, clinical trials should start with narrower, better-characterized subgroups where benefit–risk ratios are more clearly understood. Early-phase trials, in particular, should incorporate independent safety monitoring boards and enhanced interim analysis checkpoints to allow for proactive course correction.
The sector’s credibility will increasingly hinge not just on the novelty of its science but on the rigor of its implementation. Companies that build safety into their development culture, not just their trial protocols, will be best positioned to weather future scrutiny.
For CDMOs and Technology Partners
Contract manufacturers and enabling technology providers occupy a pivotal role in the gene therapy supply chain, and their contributions must now evolve beyond throughput and scale. The demand is growing for vector engineering platforms that can address the specific risks spotlighted by the Sarepta experience, particularly liver toxicity and innate immune activation. Capsid modifications, tissue-specific promoters, and dose-sparing innovations are not just scientific enhancements; they are risk mitigation strategies with direct regulatory relevance.
CDMOs that support their clients with integrated regulatory risk modeling, particularly linking CMC decisions with clinical development and long-term safety considerations, will become more valuable strategic partners. This may involve early collaboration on patient stratification models, vector biodistribution studies, or adaptive manufacturing protocols that can accommodate evolving safety data or population-specific formulations.
As regulatory expectations shift, CDMOs will need to become more agile, both in process design and in how they support clients navigating uncertainty. Those that can demonstrate technical excellence alongside strategic foresight will help lead the industry through its next phase.
For Investors
Investors are recalibrating their criteria in the wake of recent events, and for good reason. The past decade encouraged large bets on single-product gene therapy companies based on platform potential, accelerated approvals, and speculative upside. But in a market where safety can reset value overnight, the emphasis must shift toward durability and diversification.
Companies with multiple therapeutic strategies — not only across indications but across modalities — are more likely to withstand regulatory disruptions or trial setbacks. Innovation alone is no longer a compelling pitch; it must be paired with clinical execution and operational discipline. Transparency, especially in adverse event reporting and trial communications, has become a marker of credibility.
There is also new opportunity in adjacent sectors. Companies working on delivery systems, vector optimization, or immune modulation strategies may be poised to benefit as the industry retools its foundational assumptions. Investors who can identify and support these enabling technologies may find returns that are not only stronger, but more resilient.
For Regulators
The FDA and other global regulatory bodies have a delicate role to play: restoring public trust while continuing to facilitate access to transformative therapies. One clear area for improvement is the formalization of platform designation guidelines, particularly outlining when and how such status may be revoked. This would help developers better understand the contingencies of regulatory flexibility and reduce reliance on assumptions that may not hold across programs.1
Regulators might also consider implementing tiered warning structures or labeling frameworks that evolve with accumulating safety data. A static label applied across all patient populations can obscure important risk differentials and limit clinicians’ ability to make informed decisions.
Finally, harmonization across regulatory jurisdictions will become increasingly important as adverse event data, real-world evidence, and post-market safety signals emerge from global programs. Standardized reporting practices, shared pharmacovigilance systems, and cooperative regulatory reviews could help prevent future crises and build a more coherent global approach to gene therapy oversight.12
All of these measures point toward a sector growing up. The scientific tools are still powerful. The unmet need remains vast. But the path forward must be walked with greater humility, vigilance, and coordination than before. Gene therapy does not need to be perfect to succeed, but it does need to be accountable.
Conclusion: A Crisis of Confidence, Not of Capability
The challenges facing Sarepta Therapeutics are serious, and the consequences of its missteps have reverberated throughout the gene therapy sector. But to interpret this moment as a wholesale indictment of genetic medicine would be to confuse a crisis of execution with a failure of potential. The setbacks are real: lives were lost, public trust was damaged, and regulatory protections were tested. Yet the underlying science that supports gene therapy remains sound, and the therapeutic needs it seeks to address are as urgent as ever.
What this crisis has exposed is not a flaw in the idea of gene therapy but a breakdown in how that idea has been operationalized. Overpromising, underreporting, and overreliance on assumed regulatory pathways created vulnerabilities that could no longer be ignored. The future of the field now rests not on how quickly it can return to the status quo, but on how willingly it embraces a higher standard of accountability, transparency, and scientific rigor.
Gene therapy’s promise is still within reach. Its capacity to deliver durable, potentially curative treatments remains unmatched in many disease areas. But there are no shortcuts left. If the sector is to regain the trust of regulators, investors, clinicians, and. most importantly, patients, it must earn that trust deliberately. That work begins now, but the industry is well positioned to execute it.
References
1. FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold for Multiple Gene Therapy Products Following 3 Deaths. U.S. Food and Drug Administration. 18 Jul. 2025.
2. Walker, Joseph. “Sarepta Therapeutics Stock Plunges After Another Patient Death Is Linked to One of Its Gene Therapies.” Wall Street Journal. 18 Jul. 2025.
3. Perrone, Matthew. “Sarepta will resume gene therapy shipments after FDA review of recent patient death.” Associated Press News. 28 Jul. 2025.
4. “Sarepta's 27% Sell-Off Is 'Overblown,' 'Overdone' And 'Overly Bearish.' Here's Why It Happened.” Jar of Hope. Accessed 1 Aug. 2025.
5. FDA Informs Sarepta That It Recommends That Sarepta Remove Its Pause and Resume Shipments of ELEVIDYS for Ambulatory Individuals With Duchenne Muscular Dystrophy. Sarepta Therapeutics. 28 Jul. 2025.
6. Gatlin, Allison. “The FDA Will Reportedly Ask Sarepta To Stop Selling Elevidys. Shares Plummet.” Investors.com. 18 Jul. 2025.
7. Nathan-Kazis, Josh. “Gene Therapy Was the Biggest Idea in Biotech. Now It Has Lost Support on Wall Street.” Barron’s. 20 Jul. 2025.
8. Kilgore, Tomi. “Sarepta finally gets some good news: A patient death wasn’t its DMD drug’s fault.” MarketWatch. 29 Jul. 2025.
9. Ellison, Ayla, Fraiser Kansteiner, Angus Liu, and Gabrielle Masson. “Untangling Sarepta’s gene therapy fallout and a growing trust deficit.” FiercePharma. 1 Aug. 2025.
10. Blake, Oliver. “FDA Safety Scrutiny and the Future of Sarepta Therapeutics' Gene Therapy Portfolio.” AInvest. 25 Jul. 2025.
11. Hale, Victor. “Assessing the Long-Term Viability of Sarepta Therapeutics Amid Regulatory and Safety Crises.” AInvest. 27 Jul. 2025.
12. Nathan-Kazis, Josh. “Top FDA Official’s Surprise Departure Means More Uncertainty for Biotech.” Barron’s. 30 Jul. 2025.