The FDA recently approved SAPHRIS (asenapine) for the treatment of both schizophrenia and bipolar disorder. It is available only as a sublingual tablet, meaning that it is not effective if swallowed, and it must be left under the tongue to dissolve for it to be absorbed into the bloodstream. I haven’t yet reviewed the studies to see if SAPHRIS has any advantages over other antipsychotics, but I do know that Jeffrey Lieberman, MD, who is Chair of Columbia University Department of Psychiatry as well as the head of the APA's Council on Research, was quoted in this article as saying that “The studies haven’t shown that [SAPHRIS] provides any unique therapeutic advantage. The main contribution is that clinicians and patients will have yet another choice.”Advantage or not, Schering-Plough is already poised to make aggressive use of hired guns to get psychiatrists to prescribe its new antipsychotic.
Oddly, the company just sent me a SAPHRIS Speaker Bureau invitation packet. I guess my 2007 New York Times Magazine memoir describing the tangled ethics of promotional speaking has not yet become required reading at Schering-Plough.
Their invitation packet starts with this cover letter flattering me by saying, “As a recognized thought leader and well-respected healthcare professional among your peers, we are seeking your participation as a speaker in our Schering-Plough SAPHRIS Speaker’s Bureau….”
Then there is this Speaker Bureau Agreement in which you have to promise to go to a Schering-Plough training meeting (it’s not so bad—you get $3000 plus all expenses for a day and a half meeting), and in which you promise to use only company-sponsored information for your presentations.
But the meat of the packet is called Exhibit A, (part of which is pasted above) which tells you how much you’ll be paid:
--$1,600 for a 45 minute power point presentation or informal “peer discussion group.”
--$1,000 for a 45 minute web-based live presentation (you get $600 less because you don’t have to leave the comfort of your office)
--Total maximum (called “contract total aggregate”) amount that you may receive over the course of the year is $170,000.
Evidently, Schering-Plough is confident that it can attract all the hired guns away from both Eli Lilly and Pfizer, both of which have either started posting physician payments on the web (Lilly) or have promised to do so (Pfizer). Presumably, chastened doctors will be more likely to whore for a company that will keep their payments discreet. But the impending Physician Payments Sunshine Act will prove the old maxim, "you can run, but you cannot hide."
Oddly, the company just sent me a SAPHRIS Speaker Bureau invitation packet. I guess my 2007 New York Times Magazine memoir describing the tangled ethics of promotional speaking has not yet become required reading at Schering-Plough.
Their invitation packet starts with this cover letter flattering me by saying, “As a recognized thought leader and well-respected healthcare professional among your peers, we are seeking your participation as a speaker in our Schering-Plough SAPHRIS Speaker’s Bureau….”
Then there is this Speaker Bureau Agreement in which you have to promise to go to a Schering-Plough training meeting (it’s not so bad—you get $3000 plus all expenses for a day and a half meeting), and in which you promise to use only company-sponsored information for your presentations.
But the meat of the packet is called Exhibit A, (part of which is pasted above) which tells you how much you’ll be paid:
--$1,600 for a 45 minute power point presentation or informal “peer discussion group.”
--$1,000 for a 45 minute web-based live presentation (you get $600 less because you don’t have to leave the comfort of your office)
--Total maximum (called “contract total aggregate”) amount that you may receive over the course of the year is $170,000.
Evidently, Schering-Plough is confident that it can attract all the hired guns away from both Eli Lilly and Pfizer, both of which have either started posting physician payments on the web (Lilly) or have promised to do so (Pfizer). Presumably, chastened doctors will be more likely to whore for a company that will keep their payments discreet. But the impending Physician Payments Sunshine Act will prove the old maxim, "you can run, but you cannot hide."
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19 comments:
Hi, Danny--Well, that's a pretty impressive (or depressing) set of conflicts of interest for us to avoid-- so thanks for the expose!
As for asenapine, the preclinical, in vitro work looked promising, with some effects suggesting clozapine-like properties, and perhaps benefits for negative symptoms, etc. But the APA presentation by Dr. Schooler
(26-week extension phase that followed 134 asenapine-treated patients and 172 olanzapine-treated patients) did not find any advantages to asenapine vs. olanzapine, in terms of clinical symptoms of schizophrenia. Both drugs had Both drugs had a high rate of treatment-emergent adverse events (85.1% for asenapine and 74.1% for olanzapine), although serious treatment-emergent events were less common with asenapine(11.2% versus 4.1%). One small, good piece of news: there was far less weight gain with asenapine than with olanzapine (27.9% compared with 6.0% with asenapine (change 4.0 versus -1.4 kg, P<0.001. Details may be found at http://www.medpagetoday.com/MeetingCoverage/APA, which I believe is fairly reliable.
In short, a drug that might have metabolic advantages over olanzapine, but not much of a breakthrough, from what we see so far.
--Best regards, Ron Pies
That is ugly, it really is. Thanks for letting us in on a specific example of this way of doing business. Here's betting asenapine is really just another asinine drug that doesn't do anyone any good at all. ;)
#1. That's "discreet," not "discrete."
#2. I have trouble reading past the word "whore". Could you please stop insulting sex-workers, most of whom are female and all of whom would happily be doing anything else if only they could?
Thank you.
Here I outline the marketing for the drug and brief go over the publisehd literature for schizophrenia: http://chekhovsgun.blogspot.com/2009/09/saphris-its-different-without-actually.html
In the comments sections: the author of this site: http://shearlingsplowed.blogspot.com provides a follow-up to my post concerning the unpublished trials.
Doc Righteous--Thank you for your comment. I can certainly make my points without going out of my way to offend people. I've substituted the less evocative term, "hired guns." And thanks for your editing help as well.
Agree with MacGuffin (Neuropsych15) please go to Shearlings got plowed and read my ongoing comments on asenapine.
I believe this drug (and the class) is another phen-fen. If you look at the FDA short term QT studies it had DOUBLE the rate of cardiac toxicities as compared to olanzapine.
Swallowing doesn't inactivate asenapine rather it increases the conversion to hepatotoxic metabolites. As a sublingual formulation this will be pushed in children and on a dose basis we will be seeing tons of liver failure in kids, same as seen in the olanzapine (Zyprexa) pediatric bipolar database (1 in 8 kids with elevated LFTs (hepatotox) in 2 weeks) and kids dying of liver failure after 2 years. But based on the phase I studies it looks worse than olanzapine (Zyprexa) based in the summary basis of approval.
The toxic metabolite(s) is likely an N-Desmethyl 11-OH and its conjugates which is formed by CYPs 3A4 and 1A2. 3A4 is induced by cabamazepine 1A2 is induced by smoking.
Consequently they exclude carbamazepine from the bipolar adjunctive studies and the drug interaction study used a piddyly dose so you won't see the full effect.
As for smoking, they said no effect but they used chronic smokers and then gave them 1 cig to smoke when they took the tablet so of course they won't see any interaction (intentional bias). The toxicities are dose and time related and the dose in BP is double that of schizophrenia, but the safety database is in schizophrenia so it's misleading. You may say that schizophrenics smoke like chimney's but there's lots of data that the worse your Mania is the same thing happens. Consequently we're going to have the worst toxicities in the most severely ill BP 1 patients and in children.
Also there were problems with both of the 2 so called postive efficacy studies in schizophrenia and both the FDA statistician and the Clinical Pharmacologist said there wasn't adequate proof of efficacy in schizophrenia. The medical officer also changed his review from claiming that a study was failed because the active control didn't work. (There were also a several point difference in baseline values that would account for the so called statistical difference in change from baseline. Plus if you look at other FDA psych drug approvals he was promoted the day after he recommended approval of asenapine.
So what about metabolic advantages. That's weight gain which may be related to hunger effects on the 5HT5 receptor whereas diabetes appears due to direct pancreatic toxicity, a direct effect on inhibiting sugar uptake, and possibly mitochondrial effects. The weight gain is only one aspect of it and likely a red herring.
This is one nasty drug. But to tell the truth I'm now looking at iloperidone and it looks even worse. Induces psychosis, hemolytic anemia, QT prolongation as bad or worse than thioridazine (removed from market due to QT prolongation), and is likely carcinogenic in endocrine tissues. Plus it atrophies the testes and uterus and expands the cerebral ventricals due to inhibition of pGP.
Salmon
Clarification on efficacy of asenapine: I just learned that in the 12-month data on asenapine (vs. the 26 week data), the new drug showed a statistically significant advantage over olanzapine on negative symptom score, using the NSA-16: a 15.8 point reduction vs. 11 points. However, I'm not familiar enough with this scale to conclude that this difference is clinically meaningful. I would have expected a robust difference to be evident within the first 6 months of treatment...but perhaps there is a ray of light here? We shall see. --Ron Pies
P.S. I don't have anything to do with Schering-Plough, nor they with me!
What is wrong with the word "whore" when people are selling themselves for the sake of making money? In Webster's New World College Dictionary, while it does focus on prostitute and woman in the first few definitions, it does preface with "to like, be fond of, desire". So, why can't we substitute whore for a doctor who will sell his professional integrity to make $170,000 trying to convince colleagues to use a medication that is less than proven to be consistently and reliably effective for a psychiatric disorder? Seems completely accurate to do. Besides, isn't he/she screwing the public in doing this if the outcome does not improve the health care of the patient!?
And, here we go again, on the heels of Pfizer's confession of felonious behaviors including Geodon in the list of meds. As far as I am concerned, those who are apologists and defenders of the pharma industry are lame at least, and have their own self serving agenda more in the middle, and are greedy and insensitive bastards at the most.
Wrote a prescription today for perphenzine, and the patient was fairly fine with the choice.
The more things change, the more they are the same. Ironic, eh?
Some nights, my blog just writes itself.
Tonight is one of those nights -- thanks to you, Dr. Carlat (and Marilyn Mann, for redirecting me here).
Do read Salmon, over at my place, on Saphris -- it is NO joke -- this is not. a. very. good. drug.
But thanks for the levity, just the same!
Namaste
Agree with skillsnotpills regarding the "whore" thing. DocRighteous has a clever misanthrope-as-healer shtick over at her site. Maybe someone should cross post and advise her to not label someone a "prick".
Compared to her crude descriptive assignations, calling someone a whore is lame.
You don't need to cave to an anonymous PC cop. It's your blog Dan. Call a spade a spade.
Some here have missed Doc Righteous' point, which was that the post was insulting THE SEX WORKERS by comparing them to Key Opinion Leaders paid by pharma ie. what KOLs do is much worse than simple prostitution.
Reading Salmon's comments at Scherling's Got Plowed, and those of disgruntled FDA reviewers elsewhere, it would seem asenapine got an easier run through the assessment process than it should have, and that there are people within the FDA being paid by industry even before they leave.
Disgruntled has such a negative connotation. I prefer terms such as devine discontent, morally indignant, a gadfly, or even outraged.
For who is going to speak up except for those of us who feel so strongly that we are livid with outrage at the corruption and the harm we see being inflicted often times on the most vulnerable segments of society who are least able to fight back. Including (hildren, the mentally ill, elderly in nursing homes, and yes even cancer patients whey they don't tell you we have a genetic test now that will tell you if the drug won't work and will instead kill you but we won't tell you about it so we can sell more of drug ($2 B/yr total) until it comes out when we go off patent.
Upset, angry at times, Yes. But disgruntled no!
We FDA reviewers have lost our First Amendment Rights. We (the few individuals truly in the know) cannot speak to the public about what the government is really doing and isn't that the sort of political speech that the founders were most interested in protecting (Which has been eliminated by the courts and especially the Merit Systems Protection Board (MSPB)) and not the funding of politicians by large multinational corporations with hidden agendas.
We reviewers will not be silenced, but I must do it in a legal manner, unfortanately releasing documents is just too easy to track and would likely backfire.
So for now I leave you with our unofficial anthem.
For It is the mission of each true and faithful government servant.
His duty to his country... nay, his privilege to defend the Constitution by becoming a test case.
To dream the impossible dream,
To fight the unbeatable foe,
To bear with unbearable sorrow
To run where the brave dare not go;
To right the unrightable wrong.
To love, pure and chaste, from afar,
To try, when your arms are too weary,
To reach the unreachable star!
This is my Quest to follow that star,
No matter how hopeless, no matter how far,
To fight for the right
Without question or pause,
To be willing to march into hell
For a heavenly cause!
And I know, if I'll only be true
To this glorious Quest,
That my heart will lie peaceful and calm
When I'm laid to my rest.
And the world will be better for this,
That one man, scorned and covered with scars,
Still strove, with his last ounce of courage,
To reach the unreachable stars!
An FDA Reviewer
I too have trouble reading past the “W" word. Use of loaded words like that distract attention from the issue, “money-warped behavior”, focusing attention instead on the issuer, Dr. Carlat.
The use of the word “whore” reminded me of the following from the 2005 book, On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health (Oxford University Press), by Jerome P. Kassirer, MD, a former editor-in-chief of the New England Journal of Medicine.
Chapter 2, Money-warped Behavior, page 25:
“Some physicians become known as whores. Whore is a strong descriptor, but I heard if repeatedly from colleagues about physicians who tour the country for drug companies, changing their talks repeatedly to hawk the products of the company that is sponsoring their visits. Still, I held back in using the ‘W’ word until the wife of a prominent academic physician in a major medical center used it to describe her husband.”
Her husband, the woman explained, could be away for as long as two weeks at a time on pharmaceutical company-sponsored lecture circuits.
Dr. Kassirer’s book takes a measured approach: “Even if we were unwilling to overlook some of the inappropriate behavior of drug, device, and biotechnology companies, we would have to conclude that overall, the companies have produced a great many products that benefit us. In spite of this, these companies’ efforts to influence physicians must give us serious pause.” (From the Introduction, page xvi)
For a serious pause from the Carlat Psychiatry Blog’s hortatory, read Dr. Kassirer’s book. Or just read the book anyway.
For anyone who might be interested, we have three people at Crazy Meds with various forms of treatment-resistant bipolar disorder who were prescribed Saphris in addition to other medications they currently take.
Everybody liked the effects at first. Two people had to stop taking it after less than a week due to EPS, one of them also had aggravation of his manic symptoms.
One person is still on it with good results.
The taste and literal foaming at the mouth was universally despised. Given how people with bipolar II complain about Lamictal's taste that could make it a non-starter for a big chunk of the bipolar population.
Nice blog. After reading this, I'll stick with Clozaril. I know the risks of taking it...and I know it works.
Saphris is mind numbing. Probably makes it great for the positive psychotic symptoms though I wasn't on it long enough to tell, less than two weeks. I tend towards disorganization and this med did not help that at all. Might want to prescribe a nurse-maid along with Saphris. Some twitching, insomnia, irritation, agitation. I'm medication intolerant so I get all the nasty side effects but meds are the only treatment they offered besides group therapy which I tend to disrupt.
Wow. I thought I was coming to learn about this drug. Guess people would rather just blather. I want information. I am intolerant to most drugs and am seriously looking for help. However, I am shocked and stopped at the price of the drug. Who in the world ... well rich psychos can afford anything.... can afford 6-8 hundred dollars a month? That is a shame. I also have hepc and Schering sure makes treatment almost unavailable due to the price. I guess being healthy is also another thing reserved for the wealthy. Shame on the drug companies. I stil would like to find a blog to learn about the drug and not have to listen to garbage. Anyway, my two cents.
I am 32 and have been on Saphris for 3 months, I have moderate Bipolar II & severe ADHD. I build up tolerances to medication regimens fairly quickly, within a year or 2. In my 17 years as being diagnosed I have run the gamut of mood stabilizers having been taken to the max dosage because the efficacy wears down over a short period of time, it started with Lithium which I eventually dosed out at 1800mg a day, it was barely touching me. I have been on every form of lithium and then the rest. The worst being Lamictal which gave me SJS. All I can say at this point is that for the first time in a long, long time (almost a decade), I feel "even" if that makes sense. I am more organized than I've been in long while. I have less anxiety which means less benzos to quell that overwhelming sense that used to take me over almost every day. So overall I am pro Saphris, it quells the manias and the very well thought out suicidal depressions I experience, never acted on one though but have been very oh so close. So close. But for now Saphris allows to work my job that I love, take care of myself, pay my taxes and be a productive human in society. Saphris is not going to work for everyone but at least it allows me an option that works for me when many are running out. Just thought I add my 2 cents...
For insomnia and/or psychomotor retardation, read "Effects of Asenapine on Depressive Symptoms in Patients with Bipolar I Disorder Experiencing Acute Manic or Mixed Episodes," BMC Psychiatry 2011;11 (posted 08/31/11 www.medscape.com), authored by four employees of Merck, one Merck employee formerly at Schering-Plough, and one employee of Schering-Plough at the time the research was conducted.
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