One thing about Org-24448 - would it hold up to the same level of FDA scrutiny that CX-717 is currently under? I wonder if years ago the same type of 13 week primate study was done on it, or perhaps the two species they selected were rats and dogs instead of primates (?) As we know, the finding didn't show up in dogs for CX-717. And in rats we didn't see the histo finding until Cortex found a way to up the dose dramatically (they previously were limited due to emesis). So the rat doses originally used for Org-24448 likely wouldn't have been high enough to show anything.
Presumably Organon has done further studies on Org-24448 on their own since the clinical hold was announced on CX-717. But with all the secrecy surrounding the nature of the histo finding, did Cortex tell them exactly what to look for and where (or is Cortex keeping that a trade secret)? And if Organon did see something suspicious, why would they say something that might bring down FDA scrutiny?
Logically, one would think that the FDA would require similar scrutiny of Org-24448, since it is the sister compound of CX-717. So far we haven't heard of anything like that happening, though for the FDA it would only seem prudent. So I still wonder if there is another shoe to drop here.
Of course if the FDA's chief motivation in all this is to look tougher on ADHD drugs, then they might not have any interest in examining Org-24448. On the other hand, if they truly want to determine what is happening on a cellular level with AMPA upmodulation, and whether there might be some potential for a class wide effect, then the FDA should examine Org-24448 as well as CX-717. It would probably be better to get it over with now than during/after Phase 3.
