Skip to main content



) -- While there seems to be a debate related to the dystrophin being produced by eteplirsen and whether or not it has proven to be correlated with a clinical benefit, I believe the FDA guidance on accelerated approval requires dystrophin production only be "reasonably likely to predict" clinical benefit.

All of the arguments related to the size of the eteplirsen study, the statistical analysis or the debate about the natural history of the disease ignore the data. Eteplirsen is producing dystrophin in all patients after 48 weeks of treatment and has led to a stabilization of all ambulatory patients in the study over 74 weeks in the early treatment arm, and now over 38 weeks in the placebo patients. Importantly, the placebo patients were on a steep decline before eteplirsen produced dystrophin in their muscles.

To those who do not have to live with the personal devastation of Duchenne muscular dystrophy (DMD), as my family has with my son Jett, I'm here to tell you we cannot wait any longer for drugs like eteplirsen to be approved. Those not living with DMD can afford to debate the need for a more precise and definitive correlation of dystrophin and stabilization of the disease. My son cannot. The fact that eteplirsen has proven to be safe in all of these patients, including those who have now received high doses of the drug over a 74-week period, puts an exclamation point on the need for this drug today. DMD is a rapid, progressive and irreversible disorder, which makes the risk-benefit ratio of eteplirsen extremely favorable.

"The Correlation Between Dystrophin Levels And Clinical Benefit Is Poor"

-- Cowen research report, April 22, 2013.

I find it interesting that this "correlation" concern is gaining traction now,


eteplirsen has demonstrated the ability to produce dystrophin at statistically significant levels. Eteplirsen was designed to produce dystrophin in DMD patients, and the data show the drug is doing exactly that. The FDA's regulations for subpart H accelerated approval don't require a surrogate endpoint to show a "proven and confirmed correlation," only that surrogate is "reasonably likely to predict" a clinical benefit. What does "reasonably likely" mean? Does it mean a surrogate endpoint has to mirror or correlate 100%? No, it means what it says: "The drug product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity."

In the eteplirsen study conducted by

Sarepta Therapeutics


, all 12 of the patients showed positive dystrophin fibers in their biopsies. All ambulatory participants demonstrated stabilization of their walking in the six-minute walk test after dystrophin was produced by the drug. The two twin boys enrolled in the study who rapidly lost ambulation before dystrophin was produced have shown stability on pulmonary function and muscle strength. This means all patients demonstrate positive effects associated with eteplirsen after dystrophin is produced. Not some patients, all patients.

Is it reasonable to believe there was variability in quantifying all 12 of the muscle biopsies? Is it reasonable to believe there is a sampling error in all 12 of the muscle biopsies? Even though there might be variation in the amount of dystrophin in the individual patient, the data shows that all dystrophin increased over time. Despite the limitations of dystrophin variability, it is quite encouraging that all the boys displayed dystrophin production. This bolsters confidence that eteplirsen is working. Data presented at the Muscular Dystrophy Association conference this week show stabilization in the six-minute walk test along with an increase in dystrophin positive fibers, around the same time.

If the numbers confuses anyone, there is visual evidence of the dystrophin production as well. Take a look at the slide below showing the progression of dystrophin production with eteplirsen. If you look at the 48-week biopsy slide and the dystrophin positive fibers, do you believe this looks closer to the normal healthy patient biopsy (on the far right) or does it look closer to an untreated DMD patient's muscle biopsy (on the far left)? I'll bet if you asked any five-year-old DMD patient which muscle biopsy looked closer to the 48-week eteplirsen biopsy, they would pick the normal non-DMD slide.

Eteplirsen doubters contend that only with a large clinical trial involving hundreds of DMD children will we be able to collect the data needed to satisfy the regulatory system. But let me tell you, during the face-to-face discussions I and other other DMD advocates had with the FDA (including Commissioner Margaret Hamburg) were were told repeatedly that the agency wanted to see smaller, innovative trial designs that targeted the underlying cause of the disease. FDA is aware of how quickly DMD patients progress and it doesn't want large-scale clinical trials for this disease. It was my sense that the FDA was willing to be flexible and eteplirsen might be the opportunity FDA was looking for to demonstrate their proactive demeanor in accelerated the approval of drugs for diseases like DMD.

At the end of the day, the data speak for itself. The natural history data of DMD patients is undeniable. Left untreated, those diagnosed with this disease follow a predictable decline in muscle function and walking ability. There are few outliers. The eteplirsen dystrophin data are real, the clinical benefit is evident.

Bolstering the case for the drug are anecdotal stories circulating in the DMD community. Eteplirsen patients in the Sarepta trial are beginning do to things physically they never could do before. That rarely, if ever, happens in DMD patients, particularly in this age group. These are important and measurable patient-reported outcomes where parents are seeing gains and stabilization in their DMD kids.

These gains have an enormous impact across the board -- psychologically, sociologically, economically. They are measurable, important and something the DMD "experts" have not taken into consideration. Stopping or slowing the progression of DMD spares families from having to move to a one-story house, buying a handicap van, the fitting for a power-chair or installing ramps to their home. Instead, they are celebrating things like making a basket in basketball for the first time, participating in a 5k, trying on ice skates and jumping over a bike rack to impress a girl.

My family is living with this horrible progressive disorder. We finally have the opportunity to impact this disease. How much further devastation and loss could result if this drug is not approved in the upcoming months? Far too many "experts" have lost sight of the bigger picture because they are lucky enough not to have to deal with DMD everyday of their lives. Let's be clear: DMD equals death and eteplirsen deserves accelerated approval now.

Readers might think that I'm biased and overly emotional because I want this drug to work for my son. Actually, I'm capable of evaluating clinical trials just like anyone else, I have been doing this work for 12 years, I have evaluated many potential DMD treatments. I wouldn't be as passionate about eteplirsen if I wasn't convinced it works. I have seen the benefits of eteplirsen with my own skeptical eyes. Eteplirsen works.

McSherry owns stock in Sarepta Therapeutics.

Christine McSherry is a registered nurse and co-founder of the Jett Foundation, a non-profit organization raising money and awareness to find new treatments for Duchenne muscular dystrophy (DMD). McSherry's oldest son was diagnosed with DMD. She has worked in the DMD community for nearly 13 years. While funding research in Duchenne, her organization also funds unmet needs in the community.