Despite an EU approval just a couple of days ago -- the US FDA has declared the Schering anesthesia drug Bridion®, or sugammadex, "not approvable". I'll have much more shortly (including a shiny original graphic -- DONE! -- see at right), but here is the Marketwatch story. Off 9 now 7.5 percent in NASDAQ pre-market trading (small volumes, though, to be fair). Wow.
[I'm tempted to say "told ya' so" -- with my earlier prediction for FDA approval of sugammadex coming in 2009 -- but I won't. He~He!]
It seems the FDA wants additional data on allergic reactions -- and while that doesn't directly point to concerns about efficacy -- it does portend a rather substantial additional delay. As I mentioned last night -- it seems deficient data sets out of Schering are an emerging theme -- first from two Congressional Committee Chairs, now FDA. So much for that "bump" to Schering EPS in 2008 -- or even 2009(?). That would-be $600 million market just became about $200 million, for the foreseeable future. Said another way, the 2.4 cents in EPS pick-up I posited two days ago just became one shiny penny. Just one cent of EPS, for the foreseeable future. Ouch.
Friday, August 1, 2008
FDA: Schering-Plough's Sugammadex, or Bridion®, is "Non-Approvable"! -- Ouch!
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6 comments:
Thanks go to reader Marilyn, for correcting my oft-repeated mis-spelling of the drug's name, above, and below.
[I've even had to rework the image. Sheesh! -- wake up.
Confidential Note to Self -- let your coffee take effect before typing, and then rastering, and THEN running off to meetings for a half-day. . . .]
Thanks Marilyn!
How friggin messed up is the Hosp Div?
FDA throws "Bridion" back in SGP's face just 2 weeks after the company reorganized the hospital force. So now, no drug, too many reps for the products they do have and they eliminated over 50% of the people who knew how to sell their cardiac product. So now you have lost that momentum as they'll need to teach the remaining folks about the drug. Plus, they have to rebuild relationships from the floor up when they had them already established.
WILL NO EXECUTIVE HEADS BE "REORGANIZED" AS A RESULT OF ALL THIS MISMANAGEMENT? THIS IS A CORPORATION THAT CAN'T SEEM TO UNDERSTAND THE BUSINESS THEY PURPORT TO BE IN. PENALTIES NEED TO BE PAID FOR SCREWING UP A MEAGER PIPELINE BY THOSE MIS-MANAGING!!!
I wonder what FDA actually means by "allergic reactions".
A true allergic reaction involves and immune response, however when I did a quick search on Sugammadex I found some rather interesting information.
To help you understand open up the following site http://en.wikip
edia.org/wiki/Sugammadex' and look at it while you read my comments.
Notice how Sugammadex binds rocuronium. Well rocuronium, is another Organon drug that's the subject of a whistleblower suit due to it's causing potentially lethal bronchospasm. See Ed's article at Pharmalot http://www.pharmalot.com/2008/04/organon-covered-up-raplon-side-effects/ from last tax day.
Well the bond between Suggamadex and rocuronium forms a carbamyl, vecuronium and pancuronium form similar bonds.
Although these are acetylcholine receptors they are structurally very similar to acetylcholinesterase inhibitors.
This is where it gets interesting.
Pralidoxime is a an antidote used in poisoning with acetylcholinesterase inhibitors, (e.g. Nerve Gases, Insecticides, adn drug overdoses) however it's contraindicated with acetylcholinesterase inhibitors that can form carbamyls, (similar to sugammadex). In fact in the early 1990's FDA withdrew approval of pralidoxime in children because of potentially lethal bronchospasm.
For anaphylactoid reactions the most severe form of allergic reactions bronchospasm and suffocation is the main concern.
Now if a patient had bronchospasm and problems breathing it could be misinterpreted as an allergic reaction where actually it might actually be a toxic reaction given the right set of circumstances in the body.
If it is a toxic reaction rather than an allergic reaction then the typical treatment for anaphylactoid reactions may not be appropriate and a different approach may be needed. There's also the possibility of a secondary delayed paralysis if a high enough initial dose isn't given. This is known to occur with both sugammadex and with pralidoxime and occurs after the patient has appeared to recover and then begins to move around. The treatment for this would be to give more sugammadex which would require getting the anesthesiologist having them placing the patient back on a respirator while in the recovery room.
Also I wonder how much clinical benefit this really is. A number of years ago sufentanyl came on the market to replace fentanyl (an opioid anesthetic agent) as it wore off quicker. But the actual amount of time was only 6 minutes quicker. So is sugammadex only going to result in a minimally faster offset so the anesthesiologist can move on to the next surgury quicker and make more money, while at the same time havingit result in delayed bronchospasm in some patients (e.g. those who are obese or who are on other drugs that compete with binding for sugammadex) so that the recovery room nurses have to deal with a potentially lethal reaction.
Now this is all speculation and I don't know anything. I just happen to know something about basic pharmacology and I wonder.
Salmon
P.S. It neuromuscular paralysis a really horrible way to die. You're paralyzed you can't breathe and can't move so you can't signal or tell anyone you're in trouble. But you're fully cognizant of what's going on.
On the other hand many times after surgury you kind of drift back and forth in and out of sleep. So you could just happen to die in your sleep, although the increased CO2 may kick in a breathing response and wake you up, but if you're paralyzed I doubt that's going to help much.
Like I said I don't know anything other than what I read on the internet. I just wonder.
Salmon
"It seems the FDA wants additional data on allergic reactions -- and while that doesn't directly point to concerns about efficacy -- it does portend a rather substantial additional delay."
That data will be forthcoming sooner than you might think. Since Suggamadex was approved by the EU, within a few months or so it will be available for general use in those countries. After hundreds of thousands of doses are administered, it will be clear if there are any significant adverse drug reactions, and if so, how often they occur.
- Doctor Dan
I went and looked at the FDA advisory committee info on Sugammadex and while there were over 20 cases of what I expected the allergic reactions were not among them.
The type of reaction I mentioned is typically due to inadequate dosing and there are implications that this may have been the case with Sugammadex earlier in development.
What's really provoking however is the emphasis on cardiac toxicities and skeletal toxicities, and it still being bound to bone 6 months after it was administered and the concerns with pediatric growth. Also a cyclodextran like sugammadex is going to scoop up a lot of other things like endogenous compounds, other drugs, and metabolites and change relative exposures and toxicities. It's kind of typical for FDA and companies to not point to the true concerns at these meetings. (They're required for NMEs now).
The other thing I noticed is the the number of subjects studied appeared really small. Plus the second indication for rapid rescue (directed especially at children) might have been an afterthought in order attempt to salvage an approval and get it on the market so it could be used offlabel if the other indications didn't make it.
Also cyclodextrans are being developed as a way to administer a wide variety of insoluble drugs like anticancer drugs. If a single cyclodextran were approved that pointed out a lot of problems for the class before all these other compounds were approved it would make a lot of companies mad.
FDA doesn't only have to keep SP happy they have to keep the rest of Pharma happy and better to tic off one company than tic off 20. Plus FDA can always approve it later.
Of course all this speculation I really don't know what's going on. But unfortunately this is how things tend to work with Big Pharma.
Salmon
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