Regulators overseeing rare disease treatments need better tools to weigh competing risks in real time. Sarepta Therapeutics’ Elevidys is a prime example of why.
The FDA needs two things to keep people safe: confirmatory science and updated population-specific decision-making protocols. In the absence of these, patients may be at risk. This dilemma came to light in July 2025 when Sarepta’s Elevidys was temporarily pulled from the market, leaving patients with Duchenne muscular dystrophy (DMD) high and dry.
Following the deaths of two nonambulatory patients taking the gene therapy and of a participant in a trial testing an investigational treatment using the same AAV vector for a separate disease, the FDA requested Sarepta halt all Elevidys shipments.
But this request did not account for the fact that there had been no new or changed safety signals in ambulatory patients taking Elevidys, according to Sarepta. Heeding the FDA’s stop-shipping order meant that ambulatory patients, who had been receiving the therapy for years without similar safety signals, could no longer access the medication.
The FDA followed its protocols, but the actions taken put ambulatory patients at risk, as no other gene therapies for DMD were available. These events cast an unwanted spotlight on a regulatory system that was not properly equipped to manage a highly nuanced situation unfolding in real time.
As a healthcare communications professional with two decades of experience in regulatory strategy, I’ve watched the FDA and industry navigate label updates, boxed warnings, product recalls and other challenging situations. The Sarepta case laid bare the impossibility of managing risk for patients taking gene therapies for rare diseases when the regulatory framework was designed for traditional drugs.
An upcoming bipartisan Senate hearing on February 26 regarding the authorization process for rare disease therapies is an opportunity to shape the future of regulatory oversight by proposing new protocols. With clearer frameworks, the FDA can act quickly on safety signals while minimizing harm from both treatment risks and disease progression.
Binary Choices for Heterogeneous Risks
“Halt all shipments” or “allow all shipments.” These were the options the FDA chose to work with when acting on the Elevidys safety signals. Neither was in the best interests of all parties, because they didn’t account for varied benefit-risk profiles in ambulatory and nonambulatory patients.
While the FDA knows heterogeneous rare disease populations present unique regulatory challenges, it doesn’t have specific protocols for emergency population-specific restrictions. In a peer-reviewed study in the journal Molecular Therapy: Methods & Clinical Development, the authors acknowledged this problem, writing that there is a “mismatch between traditional regulatory paradigms and the distinctive nature of rare disease gene therapies.”
While the FDA can implement population-specific restrictions through labeling modifications and REMS programs, standard protocols for deploying these tools are designed for routine safety updates in common diseases with alternative treatments, and not emergency responses related to rare disease therapies, where heterogeneous populations face dramatically different risks, and the treatment in question is often the only option for patients.
The regulatory playbook hasn’t caught up to the science, and now, new topline three-year data from Elevidys’ Phase 3 EMBARK study validate the need to revisit this conversation.
EMBARK As Proof-of-Concept for Population-Specific Regulatory Oversight
Nobody expected the FDA to be clairvoyant. The agency couldn’t have known then what EMBARK—which tested Elevidys in ambulatory patients—would later reveal. But now we’ve seen data showing a 73% slowing of disease progression over three years in ambulatory patients, a 70% improvement in the 10-meter walk/run test, and evidence that treated patients are still standing and walking after three years, with a statistically significant benefit (p=0.0002). EMBARK also showed no new treatment-related safety signals across 1,200 patients over three years.
This population-specific evidence shows that the FDA could have implemented a more nuanced regulatory response that protected patients succeeding on therapy. But halting shipments to all patients meant that ambulatory children could not be treated during the pause. This also meant losing a disease-modifying window of time that EMBARK data prove is clinically meaningful. That time is not recoverable, making it even more important that protocols used for rapid safety responses fit rare disease contexts where population-specific risks matter.
A Path Forward
Here, I recommend four proposed reforms for real-time risk management.
1. Population-Stratified Regulatory Actions: The FDA should have protocols for implementing restrictions by subpopulation in emergencies involving rare disease therapies. If liver-related deaths occur in nonambulatory patients with DMD, there should be a clear pathway to pausing shipments for that population only. When risks are population-specific, restrictions should be too.
2. Accelerate Labeling Updates: The process of adding boxed warnings can take months. The FDA should be able to mandate updates that prescribers must review before each administration. Extending accelerated labeling mechanisms to gene therapies would let regulators bridge the binary gap between “continue as usual” and “stop everything.” These are the nonspecific options that exist for a broad category of traditional, small molecule medications for common diseases with relatively homogeneous patient populations, rather than specialized gene therapies for rare conditions.
3. Amend the “Do Nothing” Risk Assessment: Regulations must account for both sides of the risk equation. Without therapy, Duchenne patients face certain progressive, irreversible muscle loss, leading to wheelchair dependence, respiratory failure and premature death. Safety standards don’t need to be lowered to ensure both sides of the risk equation are accounted for.
4. Institute Real-Time Data Sharing Agreements: The FDA and industry should update protocols for exchanging emerging safety signal data. If Sarepta had been able to provide population-specific safety data, the FDA might have implemented restrictions within 48 hours instead of a 6-day pause on Elevidys for ambulatory patients.
Protecting Patients Requires Intuitive Systems
The FDA was right to investigate the Elevidys-linked deaths in 2025. Sarepta was justified in advocating for continued access for ambulatory patients while the agency reviewed safety data. The EMBARK results prove that two things can be true at the same time: Elevidys fundamentally altered the Duchenne’s trajectory for ambulatory patients, while nonambulatory patients may face different risks. A modern regulatory framework should be sophisticated enough to account for both realities simultaneously.
A population-stratified regulatory protocol isn’t optional. It needs to be implemented to ensure patients never lose access to an effective gene therapy because of risks that may not apply to them. The FDA needs protocols that allow population-specific safety responses in real time, moving beyond binary choices that force regulators to either halt all access or continue unchanged.
As Senators convene on Thursday for this critical discussion, they must come away with a clear resolution that protects patients from both treatment-related safety risks and the certainty of disease progression. The committee should ensure that people living with rare diseases never lose access to treatment because of risks that may not apply to them. This means creating a regulatory review protocol for heterogeneous populations so that the FDA can act quickly to investigate safety signals in select patients while minimizing unnecessary risk to those who are benefiting from therapy.
