Replies to post #562 on Soligenix Inc (SNGX)

[io_io]

The evidence is that with Orbec there will be perhaps an extra 10%-15% more long-term survivors from these stem-cell transplant procedures. If not, they will die.

Here's a July 4th special, it'a a 2003 paper from Germany, people can download the PDF in the top right corner.

http://jco.ascopubs.org/cgi/content/full/21/14/2747

It's in non-myeloablatives for CLL. The paper concludes:


However, of greater concern than the acute chemotherapy-related toxicity after HSCT is the morbidity and mortality caused by acute and chronic GVHD. Despite intensification of GVHD prophylaxis by the combination of CS with short-course MTX or MMF, GVHD still remained the major problem.

And:

This was particularly true for patients with unrelated donors.*

(* where Orbec showed something like a HR of 9.0 in a sub-group analysis)

[jb_118]

The other panel members said prophylaxis would be the way to go. That means they were on board that you couldn't run another trial in acute.

The panel was there to discuss and to cast a vote on whether Orbec showed substantial efficacy, as defined by Pazdur and the FDA. They overwhelmingly voted no. If it isn't the standard of care, and it hasn't objectively proved efficacy, there isn't an ethical concern running another trial. McDonald says his IRB wouldn't approve a trial vs. placebo, but i'm not sure how heavily to weigh that point. There isn't an approved drug to use outside the scope of a trial, so where's the ethical concern? (we can discuss in a different thread the slurry docs are supposedly making to imitate Orbec in another post, but that was a strange issue that wasn't thoroughly discussed).
lacebo.

The panel was not there to tell the company how to proceed with drug development. That's between the agency and the FDA, and it's not what the panel came prepared to discuss. My impression was there was little if any substantive discussion on that point from the panel. There was some discussion between Pazdur and McDonald when he claimed another trial was impossible, to which Pazdur said he was open to negotiation, but that clearly wasn't the issue anybody from the panel or the FDA wanted to discuss at that meeting.

As far as his comment about thinking differently about the drug as a result of the discussion, I put that in context. He was responding to a somewhat pointed question from Maha H. about why he bothers to assemble a panel when it's clear to her that a miss on the primary endpoint is a fatal flaw from the FDA's standpoint. His response was justification for calling a panel by saying it helped with his understanding of the drug. What else could he have said? We called you so we can pin this on the panel so the FDA doesn't look like the bad guy and take all the heat for failing to approve the drug?

What is the risk for the FDA to approve the drug?

The risk isn't patient risk, but as outlined by Perry, if you lower the bar for orbec in terms of approval with a questionable efficacy profile, then you lower the bar for everybody. Once you do that, you'll never get the hard scientific data you need about efficacy of drugs. Everything I've seen out of the agency recently and the FDA's posture in that AC meeting leads me to believe it's an approvable. But who knows. Both DNDN decisions (AC and FDA) surprised me.