Feds Probe Cephalon For Off-Label Treanda Promotion
21 CommentsBy Ed Silverman // July 11th, 2011 // 9:51 am
Just as Teva Pharmaceuticals hopes to wrap up its $6.2 billion acquistion of Cephalon, the biotech has been asked by the feds about documents relating to alleged off-label promotion of its fast-growing Treanda medication, which is used to treat chronic lymphocytic leukemia and racked up $117 million in sales in the first quarter of the year.
Last month, Cephalon received a notice from the US Department of Justice concerning paperwork pertaining to off-label use, including use of Treanda for first-line treatment of non-hodgkin’s lymphoma (the med is not approved for this purpose - see here), according to sources familiar with the request. The feds also want clinical studies that could be used to support off-label use before the studies were completed or submitted to the FDA for review.
The feds are also interested in educational and speaker programs that reference off-label use; uncompleted clinical studies that may be used to support off-label use; documents pertaining to a clinical study being conducted by to Mathias Rummel, who is the head of hematology at the University Hospital in Giessen, Germany, and has previously studied Treanda (see this); and documents related to a study called Bright, which is designed to test whether the drug could combat advanced low-grade non-Hodgkin’s lymphoma and mantle cell lymphoma in patients who have not yet received treatment (read here).
The probe could complicate life for Cephalon, which is already operating under a so-called Corporate Integrity Agreement in connection with its 2007 plea to a misdemeanor violation of the Food, Drug and Cosmetic Act for improper marketing of several meds, notably its Provigil narcolepsy drug, which docs were prescribing to treat depression and ADHD (read here). The drugmaker paid a $375 million fine as well.
What, if any, implications this may cause for the deal with Teva is unclear. Teva, which is one of the biggest generic suppliers in the world, wants to buy Cephalon in order to blunt competition to its brand name Copaxone multiple sclerosis med and expand further into the brand-name medicine world. Cephalon, which experienced a different kind of tumult since co-founder and ceo Frank Baldino passed away last winter (see here), is developing treatments for lung cancer, congestive heart failure and asthma, for instance.
A Cephalon spokeswoman declined to comment.
Evelyn Pringle
I can hardly wait to see how the Feds handle Cephalon’s obvious breach of the Corporate Integrity Agreement.
What did that CEO die of does anybody know?
Basel lair
Off-label promo is the mother of all the misconduct bigpharma does. In fact this is what the bigpharma misconduct is all abut. What ever they do unethiclly and criminally it has to do with off-label promotion in the end. For those who don’t know much about this classic bigpharma crime, it is the best and easier way to make those huge EXTRA profits they so geedily crave. The biggest advantage of off-label is that by promoting the unapproved indications they don’t have to bother spending all those millions proving that off-label indication is safe and effective.They get approval for the new drug on the easiest to prove indication and then the sky is the limit. Even in US where they pay huge fines if cought, they do it over and over again. They will never stop till some of these crooks that play with patients’ lives, end up in jail for a loooong time. Also till the gov’t hits them so hard as to close the place down, period. That can not happen in a USA style of biz environment where the biz is everything and gets literaly unconditional support from both parties, esp. the republicans. Yes the biz is paramount and the victims of it are just disposable customers.
Lori
The former founder and CEO of Cephalon, Frank Baldino died of Leukemia shortly after he was diagnosed.
John
I’d have to agree that off label marketing is a bad idea for the reasons you provide: it short circuits the entire FDA approval process.
On the other hand, though, the pharmaceutical industry is one of only a handful that can’t sell anything without getting the sign off from a third and sometimes a fourth party. If the MDs are simply patsies for whatever a sales rep tells them about off-label use of a drug, they’re seriously overpaid. If they’re not, then there is presumably some basis for the Rx being written. And then if its an expensive drug, it probably doesn’t go out too often without an insurance company committee deciding if it is medically justified.
It would be nice to have a quarter as many safeguards in the marketing of nutritional supplements. I can walk down the aisle of my local grocery store and find dozens of products that are claimed to provide “male enhancement”, diet- and exercise-free weight loss, and protection from Alzheimer’s disease. And as a medicinal chemist, I suspect that a lot of these are chronically toxic at the recommended dose.
John Galt
Following the rule of the FDA is unethical. In cancer therapy the FDA is horribly behind the standard of care and if physicians only followed approved indications it would be the PATIENTS that suffered.
Only an intellectual midget could think that the only “correct” way to disseminate clinical information is through the FDA approval process. If the desire of industry is to gain larger sales of their products it is imperative that patients have good outcomes resulting from the use of their products.
It is in the rational self-interest of the company that appropriate patients receive therapy that gives them the best chance of an optimal outcome. Short-term gains from patients receiving the wrong therapy will ultimately reduce the overall use of the therapy.
It is the Ivory Tower syndrome of bureaucrats in Washington, DC that think that only THEY have the intelligence and objectivity to judge the risk/benefit of a therapy. Surely, a clinician in the community is a mere stooge at the hands of evil pharma and must be protected.
United Healthcare has refused to pay for therapy using Treanda as single agent therapy. This is because United Healthcare follows NCCN Guidelines-THE authority in the standard of care for cancer therapy. It is a sad day, indeed, when an INSURANCE company is more in tune with the standard of care in cancer therapy than the FDA.
It is time to recognize that the benefit of cancer therapy is life and death, not a rash or a facilitator of an erection. The industry should be allowed to share substantially proven clinical information even if it is not blessed by the powers that be in Bethesda.
I call for Congress to act, passing legislation protecting the industry for clinical promotion of cancer therapy in line with the standard of care-the NCCN Guidelines.
Basel lair
John says “short term-gains from patients reciving the wrong therapy..” First offlable use of drugs leads often to severe side effects and also deaths. Secondly it is for huge short and long terms gains for the company that does it. Just look up Ms. Pringle’s article on Nurontin that was pushed off-label for depression that brough perhaps a billion in extra sales to Pfizer. Eventyually they paid some $430 million in fines after the whistleblower did the right thing.
To be fair to doctors, they can use any drug for any ndication they want, as long it is their decision and their responsibility. They have excess to scinetific data and if it satisfies them they can go ahead. What we don’t want to see these greedy bigpharmafia companies going out and actively promote off-label indication thus increase offlabel use to millions of patients who should be treated with proven drugs for that indication first.
How many patients took to make up that billion in Neurontin offlabel sales? Some died too.
harpy
oh, John Galt, you teabaggers are so enthusiastic and yet so misguided at the same time. it always amazes me how one can be so convincingly and breathtakingly wrong. now, wipe the spittle off your chin and let’s talk.
1) following the FDA is not unethical.
2) no one said FDA’s approval process is the only “correct” way to disseminate information. it is the only legal way. if doctors want off-label information on drugs, there are legal means to acquire it.
3) time and again, pharma has marketed products for purposes that have not been approved and that have injured or killed patients. and they have lied about it.
4) the “evil” FDA requires pharma to prove their drugs are safe and effective. if pharma can’t do that, then they shouldn’t sell the drug for that indication. doctors don’t have time to run trials for every drug on the market.
5) this paragraph makes no sense. “single agent therapy” for what?
6) if a therapy is clinically proven, apply for approval for that indication.
7) huh, and here I thought you were talking about the benefit for patients. sigh
anyway, I know this is a lost cause and you probably hate the USDA and OSHA and all the other government agencies that try to protect us (as in you and me), but I thought I’d try.
Factoid
75% of off-label prescribing has no science at all to justify the indications, some are for indications specifcally contradicted by scientific studies, some of those studies have been suppressed by company, getting a “peer-reviewed” journal to publish something is not hard–especially of you’re hiding what will not be published.
Some call it liberty. Some call it scuzzery.
Salient point
John-Not sure how this proposal works. Both houses of the legislature–somehow–agree to pass this & then the president signs it into law, even though it essentially means that the executive branch will be taking orders from the legislative? Seems unlikely, no?
Observer
Salient - the process is that the legislative branch writes the law - and the Executive branch enforces it. (We’ll leave out that the president has to sign it into law …) In any event, that’s the way the system works.
Salient point
Observer-Thanks. I, um, know that. My point is–given that FDA is part of the executive branch, why on earth would the president sign legislation that essentially gives Congress the ability to tell FDA how to do its job?
Obama
I’m pretty sure the point is being lost that this drug is approved for 2nd line + NHL, but not for first line. There is a standard of care already established in the front line setting. That standard of care has been around for a long time and has alot of data to back it up. This drug has one study that hasn’t even been published in a peer reviewed journal yet. Doctors can prescribe it for front line therapy if they want. However, it is illegal to promote it that way because there isn’t enough data to prove it is better than the current front line standard of care, in regards to both safety and efficacy. Yes, doctors can determine if it works for themselves, but it takes years to see a survival benefit…so they really couldn’t come up with a meaningful conclusion within their practice. That is why a large multi-center clinical trial is necessary….because it is powered to show a statistically significant benefit. There are expert panels of Oncologists at the FDA and they determine if the data is of high enough quality to expose the much larger front line patient population to this drug. Otherwise, you run the risk of giving a more expensive, less efficacious, less safe drug or drug regimen to a cancer patient. If it was you or your family member, wouldn’t you want the tried and true given first and then utilize the leap of faith as a last ditch effort??
John
I think the truth is somewhere in between. Off-label marketing is and should be illegal, but society pays a price for keeping it so.
There is no sharp point in time, before which there is no evidence that a drug is safe and effective for the treatment of a condition, and after which there is abundant evidence. For example, in most therapeutic areas, a drug that has successfully completed a phase IIb trial has at least a 50% chance of eventually being approved in that indication. Such a drug, which has not yet met FDA approval standards, may be the best available option for many patients, while still being four or more years away from FDA approval.
We don\’t allow companies to share information about these partially proven utilities with doctors, as allowing them to do so would eliminate the incentive to complete phase III studies. I agree with this policy, and believe that the fines should be as arbitrarily large as they need to be to compel compliance. But restricting the communication of information to healthcare professionals who should be qualified to judge the quality of that information for themselves strikes me as an awfully blunt instrument for accomplishing this. I wish there were a better one.
I currently take two drugs that were first prescribed to me off-label by a doctor who I have the greatest respect for. Each has substantially improved my quality of life. One was later approved for the indication for which I use it. The other was not, and the company that makes it paid a huge fine for off-label promotion.
Factoid, I\’d be interested in seeing a reference for your assertion that 75% of off-label prescribing has no scientific basis. The doctors that I see are a lot better than that.
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I heard he died of Cancer of the blood or Leukemia in particular.
Lincoln
phase II studies are safety studies, mainly…not efficacy. They are directionally correct in regards to efficacy, but you won’t know if it is statistically the same or better or worse than the control arm until you complete one or two larger phase III studies, that are powered to show statistical significance. Unless there is a significant need in a particular disease state, this is what’s required to know for sure. These large studies cost alot of money and many companies just don’t want to pay that kind of money when they are getting all of the business off-label anyway, bc payors reimburse for the drug. Even though this case we are discussing is cancer, it is “indolent” or extremely slowly progressing and most patients live a normal length life with what is currently available for much less money. Therefore, there is no excuse for the off-label promotion in this case.
Joe Sales Rep
Cephalon executives are all crooks, they give us (I’m a sales rep) the wink wink to push this stuff and manage through fear of losing jobs by not hitting arbitrary sales goals. They rather make a billion and pay the 300-400 million dollar fine. Cost of doing buisness
whatever
the national comprehensive cancer network (nccn) has recommended the use of cephalon’s drug in the first line treatment of NHL. yes, the fda hasn’t approved it, but i think a panel of experts in the treatment of lymphoma know what they are talking about. maybe it’s not that its being promoted that way, but thats the way the standard of care is moving?
John
I\’d have to disagree Lincoln. I don\’t think I\’ve ever seen a Phase II trial in which safety rather than efficacy was listed as the primary endpoint. And depending on the therapeutic area, it is not all that uncommon to see statistical separation from placebo in Phase II.
A recent study published in Nature Reviews Drug Discovery shows that about 50% of drugs which succeed in Phase II eventually become approved drugs. Whether this is good enough is naturally going to depend on what your other options are.
Reagan
To “Whatever,”…yes, the NCCN Guidelines do have TREANDA as one “option” for front line NHL. Cephalon has given millions of dollars to NCCN over the past several years. And there’s no doubt that it is being promoted that way because the TREANDA sales force has failed several audits for off label promotion of TREANDA, as high as 15% of the time. And if you say “that’s the way the standard of care is moving,” why hasn’t the data that the NCCN guidelines used to put it in the front line setting been published yet??? Maybe because it’s bullshit? The CHOP-R arm of the Rummel study is significantly worse, in terms of efficacy, than in all other CHOP-R arms in studies that have been done. You can’t just change a 30 year standard of care with one study that hasn’t even been published yet. That was a stupid thing to say…
Reagan
To John, Phase II studies are not powered to show a statistically significant efficacy benefit…they do show directionally, so the FDA only accepts phase II efficacy data in rare circumstances where there is a significant need in the disease area for something to give to the patients. With an indolent (slow growing) NHL, there is not a significant need in the market place. It will require one or two well controlled phase III trials to get this indication or to show superiority over the current standard of care.
John
Reagan, in general we are in agreement. But here are a few counterexamples.
http://www.portola.com/pdfs/Portola_INNOVATE_PCI_ESC.pdf
http://www.seasidetherapeutics.com/sites/default/files/news_media-release_2010-09-09.pdf
http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=6f5766d8-3c8e-4325-bce5-8dcd0cb07f14&cKey=6ae1b64d-8ceb-41ef-8253-0e8a778b3a0a&mKey={10A86782-07E4-4A2D-9100-F660E5D752A9}