Conference call notes

The conference call consisted of some people from PPMD and some that work for PTC. Now, the "primary endpoint" of this study was an improvement in the six minute walk test (6MWT)-the distance a boy could walk in six minutes. There were three arms in the study: low dose Ataluren, high dose, and placebo. And the 6MWT was not looked at on an individual basis; they were looking to see if there was any statistical difference between the three GROUPS of boys, i.e. did the boys on high dose perform better than those on the low dose or placebo. And once the last boy had been treated for 48 weeks, they looked at the data and found that there was no statistical difference between the three groups. They had to shut down the study because the primary endpoint was not met-not necessarily because they wanted to, but regulations dictate that they have to.

It's kind of confusing, because even if the boys on the drug didn't improve individually, if they declined slower than the boys in the placebo group, that would still be considered an "improvement." So they weren't just looking for distances to increase, they were comparing all three groups. Even still, no statistical difference.

The reason they used the 6MWT as an endpoint rather than looking at, say, dystrophin production in the muscle or CK levels in the blood, was because the FDA requires the primary outcome of the trial be "clinically meaningful," meaning it must directly impact some aspect of daily life. Increase in dystrophin production is hard to correlate to impacting daily life, because some boys who have DMD make plenty of dystrophin but their mutation is such that the protein is non-functional. This is all important because in order to get FDA approval, clinical meaning has to be there.

So basically, the only data they have compiled right now is the results of the 6MWT. There is still A LOT of other data they need to look at, and it *sounds* like the company is committed to seeing if there is any way to go forward from here. There are a lot of variables to consider: age, steroid use, particular area of the mutation...even though all the boys have a point mutation, or stop codon, the mutations could be on different exons, or have different amino acids that were switched around, so there are subgroups to look at...so we shall see if anything useful comes out in the coming months. It sounds like it's going to be a bit of a long process. I will try to stay hopeful, but maybe a bit more realistic this time-this has really hit me hard and while it's nice to have hope, when it doesn't turn out the way you want, it's very difficult.