FDA Rejects Schering-Plough Anesthesia Drug
11 CommentsBy Ed Silverman // August 1st, 2008 // 10:45 am
The rejection of Bridion, a drug developed to reverse the effects of anesthesia, is the latest setback for the drugmaker, which is still reeling over the controversy and subsequent loss in revenue from its Vytorin cholesterol pill.
The FDA’s ‘not approvable’ letter was issued for an injectable med that was heralded as a breakthrough product unanimously recommended by an FDA advisory committee. Earlier this week, in fact, European regulators approved Bridion. But the FDA cited concerns over hypersensitivity and allergic reactions, but not effectiveness, according to Schering-Plough, which didn’t describe the allergic reactions, which theoretically could include lower blood pressure or faster heart rates.
“We are surprised and disappointed with this action, especially given that (Bridion) received a unanimous recommendation for approval by the FDA Advisory Committee on Anesthetics and Life Support in March of this year,” says Tom Koestler, executive vp at Schering-Plough’s Research Institute, in a statement.
The rejection also undercuts Schering-Plough’s decision to pay $14 billion for Organon, where the drug originated. Schering-Plough repeatedly pointed to Bridion as one of several key reasons for the deal and Wall Street analysts forecast annual sales for the drug of up to $1 billion. In an investor note this morning, Deutsche Bank analyst Barbara Ryan called the decision “very surprising, and yet another disappointing announcement from the FDA.”
“It looks like the FDA is in a bunker-down mode, with Congress all over them,” Ryan tells Reuters. “They’re taking an extraordinarily cautious approach.”
Bridion’s ability to quickly reduce residual paralysis would make recovery rooms safer — by more quickly freeing patients from breathing tubes and their inherent potential of causing harm from undetected loss of oxygen, Ronald Miller, chairman of anesthesia at the University of California, San Francisco and a Schering-Plough consultant, tells Reuters. “And because sugammadex can completely reverse a profound paralysis, it would have allowed more ideal surgical procedures,” he says.
Schering-Plough has been counting on Bridion and other products from the Organon deal to help ensure competitive future earnings growth. As Reuters notes, the drugmaker’s earnings outlook has taken a tumble after controversial study results for Vytorin, which is sold as part of a joint venture with Merck.
Bridion was approved in Europe for reversal of neuromuscular block, or temporary paralysis, induced by the widely used muscle relaxants rocuronium and vecuronium. It was shown in trials to reverse effects of neuromuscular blockade within minutes - nine to 12 times faster than the standard reversal agent, neostigmine, Reuters writes.
Neuromuscular blockade is used by anesthesiologists to cause paralysis during surgical procedures, particularly of the abdomen, chest and brain. But patients require breathing tubes until the drugs wear off or are reversed. Edward Jones analyst Linda Bannister tells Reuters it is unclear whether the FDA will require a special safety trial for Bridion, and how long it would take.
SP 2
SP, the bell tolls for thee! This decision by the FDA will rock Kenilworth again. fred will say “More layoffs - cut another 10%!” The purchase of Organon sure was another great move by our inept management team! First, the safety issues with Organon’s already-marketed drugs and now this with the crown jewel of the purchase. This company has become the laughing stock of the industry. I believe there is so much that hasn’t even been looked at by the appropriate governmental bodies. In addition, they would do well to look at how SP has been spending their marketing and sales budgets. Oh, the pearls they would find hidden in the oyster beds!
Putting the F in FDA
It’s a shame the FDA is too scared to approve drugs that can help patients, despite positive recommendations by the advisory panel. Let’s start a comments trail of important medicines that have been wrongfully denied in the last 18 months. I’ll start Bridion, Provenge, Cimzia…
FDA Defense
Remember thalidomide!!!!! The FDA stood firm while numerous other agencies caved in. That reviewer was a hero! If there are safety concerns, then the drug needs more work before it can be approved. If serious allergic reactions are possible, then that is a problem. Give me nausea before you give me death! Hippocrates says “first do no harm.”
truthman30
“They’re taking an extraordinarily cautious approach.”
Surely this should be a policy when any drug regulatory body assesses the data on drugs they propose to regulate? …
What surprises me is not that they are taking an “extraordinarily cautious approach”, what i find extraordinary is the fact that people are surprised that they have!..
All medications should be approached with extreme caution before they are licensed. If this was FDA policy from the beginning then we might not have had a Vioxx , Paxil or Zyprexa situation ..
Could the FDA, finally at long last, be beginning to realize that their job is to regulate and protect the public from dangerous medications and that all medications should be thoroughly and adequately screened for all possible risks before they go to market?..
A sublime notion perhaps…
Or perhaps not , as the case may be..
Salmon
Working in regulatory affairs I seen a fair amount.
There’s been a lot of commentary in the press recently about how overly cautious FDA has become. In fact in two cases FDA has been criticized by the companies for not approving drugs because they weren’t as efficatious as currently marketed drugs.
Plus not all the information is provided to advisory committees and even they don’t know the entire back story.
Personally I suspect that these companies aren’t telling us the whole story, (i.e. they’re not revealing material facts.)
The Food Drug and Cosmetics Act provides for 7 situations where nonapprovals have to be given, (only minor labeling issues qualify for rescinding a nonapproval), The rest require resubmissions and a complete response, i.e. there was never any basis in the law for an “approvable letter”. Not being as efficatious is not one of them.
The relevent FD&CA follows with some examples of real reasons why drugs get turned down.
Food Drug and Cosmetics Act
Sec.505 (d) Grounds for refusing application; approval of application…
If the Secretary finds… that
(1) the investigations… do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof
(We have very good reason to suspect there may be a problem but we’ll just avoid looking for it)
(2) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions
(We only studied 13 people, the drug works, who cares if we need to study 30 people to make sure it doesn’t kill more than 10% of the people who take it. N.B. Ritalin was approved for ADHD in 1963 based on treating 13 kids.)
(3) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity
(Let’s make heparin in China with no oversight, but not let the FDA inspect the plant.)
(4) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions
(The last drug like this killed people because it produced a toxic metabolite in people who have an extremely active enzyme. Our drug produces a similar metabolite so let’s not tell the FDA anything about the metabolism and let’s only study the drug in a population that doesn’t produce the enzyme that resulted in the deaths from the other drug).
(5) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, there is a lack of substantial evidence that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling thereof
(Let’s just study it for 3 weeks when we know that all everyone is put on these drugs for life, and when we know that the toxicities take 3 months to kick in. Then we’ll tell physicians in the labeling if you continue it reevaluate the patient periodically. Alternatively the FDA knows something about the safety from another drug reviewed previously that precludes approval.)
(6) the application failed to contain the patent information prescribed by subsection (b)
(7) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular
(Ex. Let’s label this drug as adjunctive therapy for use in combination with all other drugs used in the disorder but we’ll only study it with drugs B and C. Even though we know that it’s most likely to be used in combination with drug A as it’s the drug of choice. The problem is combining it with drug A is lethal so we’ll do a small single dose drug interaction study with in strapping young healthy college students it so that we can put something in the label so that it looks like the combination is safe.)
Now a nonapproval letter requires the FDA to tell the sponsor the reason. You could be very specific and quote the exact part of the law and tell them exactly what the problem is and what is actually needed to fix it. (Except for citing the section and clause that’s actually what the FD&CA requires. However, it doesn’t set clear guidelines on how to do this.
Consequently the couple of FDA managers who sign the letters on NMEs can be extremely nebulus and state the real reason as a by the way throw away sentence and just say address it and then go into several pages of discussion of some fake reason. That way the company can show it to analysts and their board and trump up the fake reason in the press. I guarentee you that the FDA Sr. Managers who sign those letters know that law to each period.
If the FDA can then somehow get the reviewer to ‘leave’ then the sponse can come back in in the resubmission with a lame explanation and FDA can dismiss the real reason.
FDA management can also assign the resubmitted review to someone else more to the company’s liking.
The hardest thing for FDA management is a reviewer who won’t roll over. Now FDA management can always overrule a reviewer, but if the reviewer has a good case they won’t. They’re too afraid to sign their names to something like that. Instead they’ll play all the types of games I’ve mentioned.
John J. Coupal
I’m concerned that all the anonymous commenters above take no personal responsibility for their claims.
Anonymity shields scoundrels as well as heroes.
Also, how can there be a typo in the lede?
Ed Silverman
Hi John,
I understand your concerns about anonymity. This is an issue I’ve grappled with since starting the site 18 months ago.
For better or worse, the reality is that there would be much less conversation if I imposed a requirement that everyone provided identification.
I agree that this provides, in some cases, unwarranted cover for individuals to throw stones. On the other hand, the pharma biz is under a great deal of pressure these days and many of my readers - at least those working in pharma - are freer to voice their opinions and concerns if they can feel they can avoid running into difficulty at work because they discussed controversial issues in a public forum.
I hope this helps, but I’m happy to discuss this further.
And where’s the typo? At the risk of sounding dim, I re-read the lede and, maybe I’m too tired right now, but I thought it was okay.
Regards
ed
John J. Coupal
Thanks for the info, Ed.
The typo is actually in the headline, not the lede, “anesthesia”.
Several commenters defending the FDA in this post appear not to be people working in pharma, but are actually employees of FDA, or of a subcontractor.
The FDA has been taking heat from many quarters lately, and it would make sense for its employees to attempt to defend FDA performance, if they could do it publicly on a blog, without accountability.
Ed Silverman
Hi John,
Okay, thanks for pointing that out. And to answer your question - I simply move too fast for my own good sometimes, which results in a typo once in awhile. Except for coding and web design, I do everything on the site and work quickly, especially on breaking news. So I’m guilty of making a mistake now and then.
Regards
ed
BP Watch
Hassan = Organizational Incompetence.
Salmon
Mr.(Dr.?) Coupal,
Makes some interesting points. Personally I would love to oblige him however Pharma employment is at will.
With regards to the FDA if Mr.(Dr.?) Coupal isn’t aware Regulatory Affairs is the arm of Pharma that deals with the FDA.
Now with regards to defending FDA that depends. FDA is a lot of different people. When I gave examples of possible reasons FDA might turn down a drug I personally was not defending FDA management. These turn downs can occur because a single reviewer stood their ground and wouldn’t cave into pressure from FDA management and with a $1 or $2 billion a year drug with an exclusivity lifespan of 15 years that’s a lot of motive and absolutely nothing should be considered off the table.
Remember the invesigations against Victoria Hampshire, and it’s not just her just look at all the investigations and retaliation cases against FDA reviewers for the past 10 years and that’s just the ones we hear about. We don’t hear about the ones where people were forced out and lost their careers and believe me there are many more of those.
Also remember 4 years ago during the Vioxx case Senator Grassley’s chief investigator came home and someone in a ski mask attacked her with a baseball bat and put her in the ICU but it wasn’t a robbery. If someone is willing to do that to someone who’s been called one of the 30 most powerful people in Washington DC then maybe others without such good connections have good reason to be anonymous.
Plus it doesn’t have to be anyone from a company. There’s a lot of disgruntled investors and I know FDA reviewers who have told me they’ve been threatened just because they work at FDA by store clerks who lost money on stocks. Then there are the threats against reviewer’s family members.
Remember information on FDA employees is public information and who works on the review when there’s an advisory committee is also public information.
I wish Mr.(Dr.) Coupal the best. I hope this helps him understand a little of what it’s like to be on the wrong (right) side of these contentious nonapprovals.