RespireRx Pharmaceuticals Inc (RSPI)

[gfp927z]

Neuro, For RD, I still think pharmas see problems designing the pivotal trials. That could explain some of the lack of partnering interest.

Since the FDA will presumably require the pivotal trial to be conducted in a regular hospital setting, on post-surgical or chronic pain patients (as opposed to our CO2 rebreathing setup), the trial would take forever, since RD doesn't occur that often. You'd have to be monitoring tens of thousands of patients in hundreds of hospitals to eventually get enough RD events to complete a Phase 3.

In addition to this 'infrequency of RD' problem, there are other obstacles in designing a pivotal trial. In opiate induced RD, Ampakine could be used as -


1) A preventive measure, given in combination with the opiate. But as you have pointed out, combo approaches are not generally well received by the FDA for approval.


2) An RD reversal agent, used instead of Narcan/naloxone. But the problem here is that if the patient is an RD crisis, the doctor won't be able to easily 'try out something new'. He's going to have to use Narcan immediately to save the patient's life.


In Propofol induced RD however, while there would still be the same problem as in #1 above for RD prevention (combo approach), as a reversal agent, a pivotal trial would be much easier, since there is no other current way to reverse propofol induced RD (no 'Narcan' available for the indication). You would still have the infrequency problem (RD being an infrequent event), but reversing propofol induced RD might be doable approach for a large pivotal trial. It would still take a long time, but might look more palatable to pharma partners than the prospects for opioid RD trials.

Unfortunately we don't have any human data demonstrating POC with Propofol, only the promising animal data from Greer. But that might ultimately be the way to go -- reversal of Propofol induced RD. And with no current treatment for Propofol induced RD, it might sail through the FDA relatively easily as a Fast Track indication, and require a smaller than usual Phase 3.