Glaxo's own safety data presented Thursday illustrate the lack of a real study blind. Almost 80% of the drisapersen-treated patients reported injection site reactions, compared to 33% of placebo-treated patients.
It's entirely possible patients who knew they were receiving drisapersen were motivated to perform better during the two six-minute walk tests performed at weeks 13 and 25. Likewise, the kids on placebo were unmotivated. It's impossible to quantify with any precision the effect of unblinding might have had on this trial, but the placebo effect needs to be taken into account.
At some point during the course of a clinical trial, the positive impact of the placebo effect runs out. Take a look at the slide again. From week 25 through week 48, continuous drisapersen patients (green line) and placebo patients (blue line) behave exactly the same. The two lines mirror each other, which suggests -- but doesn't prove -- drisapersen might be nothing more than a placebo.
What do we need to be more confident in drisapersen's efficacy? Measurements of dystrophin production. Unfortunately, Glaxo didn't bring these data to Cold Spring Harbor Thursday.Dystrophin is the protein that helps repair muscles and generally makes muscles function better. DMD patients have a defect in a gene that makes them unable to produce dystrophin. Drisapersen and Sarepta's eteplirsen are designed to "skip over" the defective gene so patients can make partially functional dystrophin. If the green and blue lines in the slide above truly demonstrate drisapersen's ability to improve walking ability of DMD, we should also see dystrophin production in the drisapersen patients and none in the placebo patients. Dystrophin was measured in this study but Glaxo says the data are still being crunched and will be presented soon. These dystrophin data are extremely important. I don't believe you can draw any conclusions about drisapersin's efficacy without them.