RespireRx Pharmaceuticals Inc (RSPI)

[gfp927z]

The Dronabinol program appears to be on solid ground and heading for Phase 3, so that's a big plus.

Looking at the Ampakine side of the pipeline, things are murkier and we'll need to get more info from Dr. Manuso at the next investor presentation. The Dec 15 press release didn't provide much detail other than to say that REMI-2 (REMI-Infusion, a model for chronic opioid consumption) showed statistically significant efficacy at the 300 mg and 900 mg dosing levels, but the REMI-1 portion of the trial (REMI-Bolus, a model for acute opioid overdose) failed to show efficacy ("CX1739 treatment did not prevent respiratory depression, nor improve time to recovery at any of the doses tested").

http://respirerx.com/respirerx-pharmaceuticals-inc-announces-data-for-cx1739-clinical-study-in-opioid-induced-respiratory-depression/


One possible problem with the design of this trial is that they tested for acute RD (REMI-1) and chronic RD (REMI-2) on the same day, with only 30 minutes separation time. They gave a big bolus infusion of the opioid to test for acute RD, and then 30 minutes later started a steady IV infusion of opioid to test for chronic RD. Ideally it would be better from a trial design perspective to test for acute RD and chronic RD on different days, rather than having the overlap of inducing RD twice over such a short period of time. Another possible shortcoming to the trial design was its being open label for the 600 mg and 900 mg arms (only the 300 mg arm was placebo controlled).

The original analysis of the trial data, reported in September, showed statistically significant efficacy in REMI-1 (acute RD) for the 300 mg arm but not for 600 mg or 900 mg arms, but unfortunately the re-analysis of the data apparently showed lack of efficacy for all three dose levels of CX-1739.

So based on this trial it looks they'll be pursuing just the chronic RD indication instead of both acute and chronic, at least using an oral Ampakines like CX-1739. There is a very potent IV/injectable Ampakine CX-1942 in the pipeline which would be better suited for acute RD due to opioid overdose, and could potentially be used instead of Narcan/naloxone, with the advantage being that the opioid's analgesic effects are maintained using the Ampakine.

Personally I'd go after Central Sleep Apnea next since the efficacy was extremely dramatic in the Phase 2a. It was a small number of patients but showed astounding improvement. Central SA is totally brain mediated (not due to an obstructive component), and Ampakines work at the exact brain location responsible for the respiratory signal deficit (pre-Botz complex). So Ampakines are a perfect fit for treating Central SA, as was demonstrated in the Phase 2a.

CX-1739 also showed good efficacy in 'mixed SA', the type of Sleep Apnea with both Central/brain mediated and obstructive components. The only potential disadvantage in using an Ampakine for Sleep Apnea is the Ampakine's potential to disrupt sleep architecture and cause a degree of insomnia in some patients. But compared to the sleep disruption and compliance problems of a CPAP device, Ampakines would be the preferred treatment for most patients.