SRPT wrap up of ignored but traditional red flags - and a new one (I was following this company in large part because I found it both fascinating and disturbing to see otherwise savvy biotechies ignoring the red flags.):
A) touting mITT (because ITT shows zippo effect)
B) trial size. 8 patients? In a single arm trial? No drug I can find or has been suggested has ever been approved on 8 patients in a single arm. For the very good reason that you'd need HR<<0.05 to reliably see the effect. (Caveat: there might be such an approval in ultra ultra orphan. I.e. Less than 100 patients per year. I haven't looked because that isn't really applicable to general ultra orphans.)
C) Touting MOA - but your human model comes nowhere close to recapitulating your animal model for the generally accepted biomarkers. In this case creatine has been the first biomarker in DMD for decades. And Etep shows great effect in mice. An effect so large it would easily be observable in even 8 patients. But, based upon company silence, isn't even showing a trend.
D) biomarker data that is touted is non-standard and clearly engineered to exaggerate. (Percent of dystrophin positive fibers where "baseline" appears to have been set individually for each patient. All you need is a little improvement or a little dispersion and, voila!, an impressively good looking number )
E) can't get a trial rolling to save their life.
F) new one: clearly focusing on advocacy (aka lobbying via patient groups) at the expense of fixing the above. And hypocritical about it too (where's the compassionate use)?
G) management shakeup. Especially one where the CEO was censured. But I put this last because this was just icing after all the above.
And, of course, I am ignoring all the more hardcore science issues like assay reliability. The above are things anyone can see.
