At Sarepta Therapeutics, we’ve seen it all. Here are the questions I believe we should be asking to move forward in Duchenne muscular dystrophy.
Momentum in Duchenne muscular dystrophy was palpable at the Muscular Dystrophy Association Scientific Congress last month. With nearly 180 abstracts focused on Duchenne alone, spanning pre-clinical research to post-market experience, the field is at an inflection point. The question now is how best to translate scientific progress and what we’ve learned about changing the trajectory of Duchenne into tangible actions physicians and patients can take today in a disease that steals muscle day by day.
As president of research & development and technical operations at Sarepta Therapeutics, I’ve spent my career focused on developing genetic medicines for rare, life-limiting diseases, including Duchenne muscular dystrophy. Sarepta has been part of the Duchenne journey for two decades. From the development of the first exon-skipping and gene therapy for Duchenne, that experience has shaped how I think about what real progress looks like as innovation accelerates.
Gene therapy is a powerful tool, and it is not without risk. Across AAV-based programs in Duchenne and beyond, the field has seen serious adverse events, including rare patient deaths. In Sarepta’s case, this was observed only after hundreds of patients were treated. These risks are increasingly understood and, in many cases, manageable, but they require continued study and vigilance as therapies move from early trials into broader use. Against that backdrop and as the therapeutic field grows more crowded, it’s worth pausing to consider not what has potential, but what’s meaningful and supported by the evidence.
When evaluating emerging Duchenne therapies, here are a few questions I believe matter most.
1. How many patients have been treated and followed for a given therapy?
Early clinical data are an essential first step, but in a disease like Duchenne, they often don’t tell the full story. Duchenne is progressive and fatal, with loss of ambulation and shortened life expectancy still part of the expected course for many individuals. In that context, the question is not whether a therapy carries risk but whether the potential benefit justifies that risk in the face of a harsh natural history.
To address urgent unmet need, we have used FDA’s accelerated approval pathway to bring Duchenne therapies to patients sooner. Even with this pathway, generating definitive clinical evidence in rare and ultra-rate diseases remains challenging. A small heterogenous patient population, variable rates of disease progression and evolving endpoint selections have made single-study or early readouts difficult to interpret. That’s why our approach has always been longitudinal and multi-dimensional—combining confirmatory trials, extended follow-up with longer-term readouts, and real-world evidence to understand how these therapies perform over time.
This approach helped our gene therapy Elevidys move from accelerated approval to full approval in 2024. To date, more than 1,200 individuals have received this one-time treatment. Across our exon-skipping therapies—including Exondys 51, Vyondys 53 and Amondys 45—more than 1,800 patients have been treated under accelerated approval. As additional clinical and real-world data have accumulated, we are preparing submissions to FDA for traditional approval of Vyondys 53 and Amondys 45.
Ongoing clinical follow-up and real-world evidence collection have been essential to understanding and communicating the benefits and variability of these therapies, and how any risks can be anticipated and managed in real-world care.
2. What does durability look like over time?
In Duchenne, every day of disease progression represents permanent muscle damage that cannot be reversed. The condition is relentlessly progressive, with predictable points of decline and loss of function over time. That reality shifts the question from whether a therapy shows a signal at six or 12 months to whether its effect is sustained and continues to matter years later, as patients reach the ages when decline is expected.
At Sarepta, we’ve now had the opportunity to observe this across hundreds of patients treated with exon-skipping and gene therapies, supported by long-term data extending out five years or more. Durability is not simply about whether an effect persists. It is about whether treatment meaningfully alters disease trajectory and slows down the disease progression over time. Do treated patients continue to separate from natural history? Does that separation widen, hold steady or fade as the disease progresses? In a highly heterogeneous condition where the age at peak function and rate of decline can vary widely, answering these questions requires time, particularly in rare diseases where patient populations are small.
But it is imperative that we continue to seek those answers. In the Duchenne treatment landscape, durability of treatment effect is not a bonus feature. It is the difference between short-term promise and long-term impact.
3. Do biomarkers align with functional outcomes and lived experience?
Biomarkers are powerful tools, and dystrophin restoration has rightly been a focus of therapeutic development. But biomarkers are not the end of the story. In Duchenne, biomarker change hasn’t always predicted functional benefits.
What matters most to families is whether a child’s disease trajectory changes, whether walking is preserved longer, whether upper limb function is maintained, whether daily life looks different over time. As we talk to caregivers and patients, they’re looking for how individuals function daily: “Can I use my cellphone? Can I feed myself? Can I continue to get off the floor myself?” The strongest evidence is totality of evidence—when biological markers, functional measures and clinician, patient and caregiver observations tell the same story.
4. What defines responsible care as genetic therapies reach more patients?
Every gene therapy carries risk, especially in early development when only a small number of patients have been treated and the full safety profile is still emerging. As experience grows, so too does the clinical knowledge and tools to anticipate, evaluate and manage those risks.
When a serious safety event emerged in our gene therapy program a year ago, we responded by engaging regulators, clinicians and independent experts to better understand risk and strengthen safeguards, including updates to the product label. We convened independent experts in Duchenne and liver health to review the totality of available data, including outcomes in non-ambulatory patients where the two deaths occurred. Their work informed additional risk-mitigation strategies, which were shared with the broader community and continue to guide how we refine clinical protocols, including ongoing studies evaluating additional immunosuppressive approaches.
When safety events emerge, progress looks like acting decisively and learning in real time: pausing when appropriate, strengthening safeguards, refining clinical responses and sharing insights so the entire field benefits.
5. Who can this therapy reach?
The true value of a therapy is how effective it is for as many patients as possible. In Duchenne, that question is rarely simple and for many patients, unmet need remains. Eligibility may depend on an individual’s specific genetic mutation, antibody status, age, stage of disease and overall health, meaning some individuals are not yet served by available options.
Expanding who can be treated requires continued learning. In our experience, this has included studying younger patients as well as those with more advanced disease and listening to physicians and caregivers to better serve the full treatment journey—from decision-making through long-term follow-up and support.
Access also depends on the availability of specialized clinical expertise. Families need experienced providers who can diagnose the disease, interpret complex treatment options and guide them through difficult decisions. Ultimately, access depends on whether the systems around a family, such as care networks and insurance coverage, put the therapy in reach.
Plotting a path forward
Over the past decade, the Duchenne community has learned that meaningful progress rarely comes in a straight line. We’ve learned that short-term endpoints don’t always capture long-term impact. We’ve learned that therapies can miss clinical endpoints if measured too early and still meaningfully change disease trajectory over time. And we’ve learned that this evidence accumulates patient by patient, year by year.
That body of learning didn’t appear overnight. It was built through years of research, clinical trials, regulatory engagement and real-world experience. Most importantly, it was in partnership with families who took part in studies not knowing what the outcome would be but believing the work mattered.
As more therapies enter the Duchenne landscape, I am hopeful. Each new program reflects how far the field has come. And each one, if developed responsibly, can contribute to the next chapter of progress.
If we keep asking the right questions—of ourselves and of one another—we won’t just move faster. We’ll move with more strategy and more purpose. And that is how we continue to change what’s possible for people living with Duchenne today, while building toward what may be possible tomorrow.
