Ann: Phosphagenics Pain Program Update , page-68

Southoz-

Thanks for your thought provoking post.

Just a couple of points. You say "The original plan was P1 straight to P3." That's not quite correct. The original plan was a Phase 2/3 approach, but at some point in 2011 the folks in Clayton got the idea that the submittal could be fast-tracked to the FDA straight into Phase 3, a position that management maintained well into 2012, even after the crystallization issue cropped up. But it was not the original plan.

As for your guess at the reason, who knows? All I know is that there isn't a shred of evidence to support your conjectures.

As for the change in strategy, I also disagree with your assessment that this is entirely internal. I believe that the change in direction is based on advice from the FDA and the advisors on two points. First that there is a market demand for an oxymorphone patch and second that the FDA approval cannot be across the board for every indication already approved for oxycodone - which I am sure was the thinking at POH back in 2011, based on discussions at that time. The thinking was that this would only be an approval of the delivery system - not of a TPM/opiate combo drug.

Showing efficacy in reducing pain was not part of the thinking - only showing therapeutic serum oxycodone levels; I'm very clear on this - it was seen as as tremendous advantage in completing trials quickly and economically.

Where we can agree entirely is that there has been a huge delay in moving the oxycodone patch into pivotal human trials. I can remember when Phase 3 was scheduled to begin in Q3 2012, or worse, that Phase 3 was to be "completed by 2013".

The reasons for the delay stemmed first from the crystallization issue, the impact of which on the program was seriously underestimated by the company from the first; the delay has been well over a year. Then came the expansion of the pain program to include oxymorphone (and an as yet unnamed third opioid).

And here we are, as you say, further from Phase 3 than we were told in 2011.

And perhaps you are right that no one really "knows" the reasons why. I think I have a pretty good idea why, however, and it has nothing to do with dosing or stability issues and everything to do with undue optimism regarding FDA requirements, combined with the formulation failure of 2011, i.e. the crystallization.

That setback was profound, not the minor issue it was portrayed as at the time.