Tuesday, October 28, 2008

A 37-Patients-Treated With Sugammadex "Seeding" Study: Will FDA Be Swayed?

Apparently scouring the bins for something -- anything(!) -- postitive to report -- our friends in Kenilworth offer up a pathetic, waifish "new hope" for getting FDA to approve sugammadex in the United States -- a truly-tiny study, that apparently broke no new ground, on any front -- save, perhaps, the PR front. And that may yet backfire.

Recall that in April, FDA declared this candidate non-approvable. Recall also that though approved in Europe, it will garner perhaps one penny of EPS, in the near term, for Schering -- anesthesia is simply viewed by surgeons, and thus used, differently (fewer cocktails -- combinations of drugs, as a routine anesthesia protocol, in surgery) in Europe (generally speaking, here), than it is in the United States (with "cocktails" galore).

So, I am surprised that CEO Hassan and crew would believe this would do anything other than (potentially) further alienate (recall finally that Mr. Hassan gave the FDA staff a Wall Street Journal front-page finger-wag/tongue-lashing, this past Summer!) the senior FDA staff. It seems rather prosaic, and transparent -- it seems an attempt to influence public opinion -- not advance science (the numbers are too small to be meaningful).

To my admittedly-biased eye, it seems that a study with only 37 patients in treatment is designed to advance a specific PR agenda -- "Gee, isn't that mean old FDA being unreasonable in declaring sugammadex non-approvable?" -- that's the messaging point just out of the spin-meisters in K-1:

. . . .In the study, sugammadex was well tolerated in the 37 patients who received the treatment, and its safety profile overall was comparable with that of neostigmine. Safety data from the study showed that the most frequently reported adverse events (AEs) for patients in both groups included procedural pain, nausea and incision-site complications. Serious adverse events (SAEs) were reported for two patients in the sugammadex group (postoperative infection and postoperative ileus) and three patients in the neostigmine group (nausea/pain/dyspnea, gastric perforation/procedural complication and postoperative ileus). No SAE was considered study drug-related. Only one patient (neostigmine group) discontinued from the study because of two SAEs (gastric perforation/procedural complication) and subsequently recovered. No cases of hypersensitivity were reported in the study.

Text of the full study titled, "Reversal of Profound Rocuronium-induced Blockade with Sugammadex: A Randomized Comparison with Neostigmine," can be found on the Anesthesiology website. . . .
Smells like desperation to me -- as many larger unhedged multi-nationals are already (only one month into the fourth quarter) warning about potential foreign exchange/currency trainwrecks, should the euro's plummet, and the dollar's sharp rise, continue into December. Schering will definitely feel this effect -- and pointing the lank finger of accusation at FDA would not be above this crowd -- even though the two have literally nothing to do with one another.


Anonymous said...

I don't think that this would alienate FDA at all especially not senior staff.

As I recall SP tried to make the argument at the time that it should be approved for a select subpopulation who would need more rapid reversal in an emergency situation. However I don't think the studies were appropriate to justify approval on this basis.

This study could be used to justify the risk and an approval for this limited indication as they're claiming a 2.7 minute offset with sugammadex vs. 49 minutes. (Could that be a typo and they really mean 4.9 minutes?)

The market for this indication is likely so tiny that most sales are likely to be for off-label usage. Not that SP would ever promote such a thing or would physicians try to save either 45 or 3 minutes so they can hurry up to the next surgery (but assuming a $1000/hr it does at up).


Anonymous said...

2.7 minutes vs 49 really is the magnitude of the difference, just check the other trial data.
It's all posted on the FDA website, even with the trials aims so you do not need to guess at those ;-)


Anonymous said...

Thanks Anon.

I should have looked things up myself. I mainly follow other therapeutic areas.

This simply looks like the publication of part of the data (rocuronium only) from study 302 that is presented on slide 102 in the document you referred to. So the study has already been reviewed by FDA as part of the original submission.

It looks like this is just a publication will help SP to hand it out to physicians eventually (the 2.7 minutes and 49 minutes in this study are about double what are seen in other studies so it makes the difference look a lot more impressive), and so the scientists can add a publication to their CV (for promotions and for job hunting). (See we did the extra work and wrote it up and published it so now can use it for marketing etc.)

This is pretty standard fair for industry to publish a phase III study like this. I'm just surprised that they did a press release. Plus the timing is interesting. Maybe it's for investors so they might say, wow 2.7 min vs. 49 min that's impressive SP does have something with this drug after all.


Anonymous said...

You were right definitely a PR campaign.

The AP is running with it.