You can be encouraged and excited about a drug (and a stock) while also being worried about unsettled risks that may blow up the entire endeavor. That pretty much sums up the current state of Sarepta at this point.

The paramount concern is the small trial size -- four DMD patients dosed at the highest 50 mg eteplirsen dose for 36 weeks compared against four "control" patients dosed with a placebo for 24 weeks followed by 12 weeks of eteplirsen. With so few patients, variability of response can muddy interpretation of results.

For this reason, the next look at the data after 48 weeks of is critically important. Some benefit observed in the six-minute walk test favoring eteplirsen over control at 36 weeks should be maintained at 48 weeks. It's okay if eteplirsen patients lose some additional walking ability, as long as the rate of disease progression observed is slower than that measured in the control group of patients.

Let's talk about the control patients for a second because they're just as important. Remember, these patients crossed over to treatment with eteplirsen after 24 weeks, so some benefit from the drug should be measurable by week 48. That means the steep rate of disease progression observed in the control patients through 36 weeks should start to ease up at 48 weeks.

This may sound counter-intuitive, but a narrowing of the walking distance benefit favoring etiplirsen patients over control patients at 48 weeks could be positive because it suggests that control patients are starting to benefit from eteplirsen as well.

A sustained benefit from a small number of patients isn’t going to be enough to assuage all doubt so Sarepta also needs to show that eteplirsen-treated patients have measurable increases in dystrophin levels --- the missing or malfunctioning protein that causes DMD. Any data that correlates increased dystrophin production to improvements in walking ability will go a long way towards demonstrating the efficacy of eteplirsen.

I mentioned in my story this week the possibility that Sarepta could seek accelerated approval of eteplirsen based on positive 48-week data. For this option to be viable, Sarepta needs the dystrophin production data to support the walk benefit. Even if all the data work in Sarepta's favor, the odds that FDA would approve eteplirsen based on this small study, even under new and more lenient regulations for orphan drugs, are small. In other words, don’t count on accelerated approval. Consider it upside. It's not a negative if FDA asks Sarepta to run another study before approval as long as the 48-week data look good.

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