Monday’s story by New York Times reporter Gardiner Harris revealed that Glaxo SmithKline (GSK) had withheld studies showing serious risks associated with the world’s former best selling diabetes drug for 11 years.
GSK withheld results from a 1999 study that they conducted comparing Avandia to its main competitor, Actos. Rather than demonstrate that Avandia was safer, this 1999 study linked Avandia to a 43 percent increased risk of heart attacks. GSK never reported these findings to the FDA, and has spent the last 11 years trying to cover them up. One GSK executive at that time even said in email exchanges that:
“Per Sr. Mgmt request, these data should not see the light of day to anyone outside of GSK.”
In fact when one GSK official asked about whether two of the drug trials in question should be published, this same executive responded:
“Not a chance. These put Avandia in quite a negative light ….”
But the case against GSK doesn’t stop there. In addition to failing to disclose these results to FDA, there is evidence that GSK researchers excluded a dozen serious heart problems in the total tally of adverse events from their 6-year ‘RECORD’ study on Avandia released in 2007.
One FDA reviewer found a number of instances where “deaths that occurred while taking Avandia were inexplicably dropped from the final analysis.”
A former manager of the FDA’s drug safety unit, Rosemary Johann-Liang, revealed in a deposition last month that Glaxo withheld from FDA other records from 2001 showing Avandia may cause heart attacks and that Glaxo did not turn over an e- mail from researchers who concluded Avandia “strengthens the signals” of heart ailments.
Does this leaves anyone else with a feeling of déjà vu? This is Vioxx all over again. In 1999, manufacturer Merck withheld studies or other data documenting the serious cardiovascular side effects associated with Vioxx. This block-buster drug rose to $2.5 billion in annual sales before its risks were revealed in 2004. Some estimate Vioxx led to 44,000 deaths and 80,000 heart attacks. While this Vioxx scandal resulted in a record-breaking $4.8 billion dollar settlement of 26,000 personal injury claims, many feel that Merck got away with murder, or at least manslaughter. And while $4.8 billion is a lot of money even to Merck, their gross sales of Vioxx were far greater.
Another example of drug industry executives putting profits ahead of patient safety.
What’s next for Avandia? And GSK?
Today’s panel at FDA will decide whether to recommend that the drug be withdrawn from the market.
GSK has negotiated over 10,000 settlements for $460 million, according to Business Week. This seems like a small amount. Certainly other cases are bound to follow.
GlaxoSmithKline (NYSE:GSK) sells a popular brand-name prescription drug for migraines, Imitrex. 2007 U.S. sales of Imitrex were $1.12 billion, making it a “blockbuster” in drug industry parlance. A single pill of Imitrex costs about $25.
Glaxo has certainly done its part over the years to preserve its market share on drugs with expiring patents and to prevent consumers from having access to more affordable generic versions, as alleged in several lawsuits that we here at PAL have been involved in (see Relafen and Augmentin, for example).
Well, $1.12 billion in annual sales is too good to just give up, right? Even if Imitrex’s patent is expiring next February? Not surprisingly, then, Glaxo has done a number of things to keep a generic version of Imitrex (sumatriptan) off the pharmacy shelves:
Later this year, Glaxo will begin selling an “authorized generic” version of Imitrex. Authorized generics really should be called “fake” generics, because they’re most often not generics at all, but the company’s own pill technically sold by a different company, under a license. In this case, the shill licensee is Dr. Reddy’s, a generic drug company that originally challenged Glaxo’s Imitrex patent and then settled when Glaxo sued them for patent infringement.
Also later this year (December 2008), Ranbaxy, another generic drug maker, will also begin selling a generic version of Imitrex. Again, this stems from a settlement between Glaxo and the generic maker.
Great, right? Two generic versions of Imitrex will be available by the end of the year! Huzzah! A victory for patients, right?
Not so fast! You don’t think Glaxo is going to let its billion dollar baby leave home so easily, do you?
Introducing GSK’s Treximet! Treximet was just approved by the FDA for acute treatment of migraines in adults.
Is Treximet a fabulous new breakthrough treatment for migraines?
Umm… No.
It is a combination of Imitrex (soon to be available as a generic) and naproxen sodium (commonly known as Aleve, available Over the Counter).
So Treximet is a combination of (a) a soon to be generic drug and (b) an Over the Counter drug. Yet you can be sure that Treximet’s price will be similar to what Imitrex costs right now ($25 a pill) and there’s a good chance it will be more expensive, as new drugs typically are ($30 a pill? More? Who knows?).
How much would it cost a patient to take these 2 drugs separately?
Naproxen sodium can be had for about 8 cents a pill. A single Aleve pill has 220 mg of naproxen sodium. There’s 500 mg of naproxen sodium in Treximet, so a patient would have to take about 2 1/4 Aleve pills to get to 500 mg. Since you can’t really take 1/4 of a pill, let’s assume most patients would take 2. 2 pills would give you 440 mg, so that’s pretty close to the 500 mg. Cost: 16 cents.
We don’t yet know how much generic Imitrex will cost. But the price of a generic typically drops to about 30% of the brand-name’s price within 6 months of the drug’s patent expiring and more generic companies introducing their own versions. So it’s safe to assume that generix Imitrex will cost about $7.50 by middle of 2009. (Even before then, the price of generic Imitrex will begin dropping from the current price of $25 a pill.) Cost: $7.50
So, by spending $7.50 on generic Imitrex and 16 cents on over-the-counter Aleve, you can get the same thing you’d get in a Treximet — which is very likely to cost $25 or more. Why would you bother with the Treximet? I guess it’s fewer pills to take, but is that worth at least $18 in additional cost?
Interesting, Glaxo apparent didn’t even try to compare Treximet to a standalone-combination of Imitrex and naproxen sodium. Their press release on the FDA approval says:
“Treximet provided more patients migraine pain relief at two and four hours compared to sumatriptan 85 mg, naproxen sodium 500 mg or placebo alone.”
In other words, Treximet worked better than just Imitrex, or just naproxen sodium, or nothing at all. This is kind of like saying that a chocolate cake tastes better than eating the ingredients separately (a bowl of flour, a few eggs, some chocolate) or eating nothing at all.
Here’s some other things I think you can safely gaze into the crystal ball to see:
Glaxo’s pharmaceutical salespeople will descend on doctors’ offices like ants at a picnic and aggressively pitch Treximet to doctors of all kinds (neurologists, headache specialists, internists and family physicians).
TV ads will appear in prime time singing the praises of this “new” treatment for migraines. People frolicking through fields of flowers may or may not appear.
Is this the kind of “breakthrough treatment” than PhRMA is always arguing justifies the high cost of prescription drugs?
This type of putting “old wine in new flasks” is straight from Big Pharma’s tired playbook. Instead of engaging in the harder, more long-term process of discovering genuinely new medications, drug companies instead “tweak” existing blockbuster drugs in the most minor of ways, including:
Combining two existing drugs, such as was done with Vytorin (made up of Zocor, which had gone generic, and Zetia)
Making a “extended release” version (once a day, once a month, etc)
Making a “new” version that’s just a chemical tweak of the original but not any better (as Nexium is of the now-generic and over-the-counter Prilosec)
A $125 million settlement has been announced in a major class action lawsuit involving members of the Prescription Access Litigation (PAL) coalition. The case, In re Pharmaceutical Industry Average Wholesale Price Litigation, was originally filed in 2002, and claimed that the defendant drug companies intentionally inflated reports of the Average Wholesale Prices (AWPs) on certain prescription drugs administered in doctors’ offices and paid for by Medicare Part B. The PAL member organizations that are plaintiffs in the lawsuit are:
Until 2006, the published AWP was used to set the price that Medicare and consumers making Medicare Part B co-payments pay physicians for these drug. Private insurance companies and other third-party payors also use the AWP to determine how much to pay physicians. The lawsuit contends that
consumers and third-party payors paid more than they should because of the drug companies’ false AWP reporting.
The settlement includes branded and generic drugs used primarily in the treatment of cancer, HIV and other serious illnesses. Under the terms of the settlement 82.5 percent of the settlement fund is designated for third-party payors’ claims and the remaining 17.5 percent is designated for consumer claims.
The defendants included in today’s settlement are:
Abbott Laboratories
Amgen Inc.
Aventis Pharmaceuticals Inc.
Hoechst Marion Roussel
Baxter Healthcare Corp.
Baxter International Inc.
Bayer Corporation
Dey, Inc.
Fujisawa Healthcare, Inc.
Fujisawa USA, Inc.
Immunex Corporation
Pharmacia Corporation
Pharmacia & Upjohn LLC
Sicor, Inc.
Gensia, Inc.
Gensia Sicor Pharmaceuticals, Inc.
Watson Pharmaceuticals, Inc.
ZLB Behring, L.L.C.
Drugs covered in this settlement include Aranesp, Epogen, Neupogen, Neulasta, Anzemet, Ferrlecit and Infed. A full list of the drugs covered by the settlement is available here.
Medicare Part B recipients, health plans and individuals who paid for these drugs but were not on Medicare will be eligible to receive payments from this settlement once the Court finally approves it. The following types of individuals and entities will be eligible:
Patients on Medicare Part B who paid a percentage (i.e. not a fixed copayment, but 10%, 20%, etc.) of the cost of one of the drugs in the case, taken between Jan. 1, 1991 and Jan. 1, 2005.
Health Plans and other Third Party Payors who paid all or part of a Medicare Part B recipient’s percentage co-insurance for one of the drugs.
Individuals not on Medicare Part B who paid all or part (a percentange) of the cost of one of the drugs taken between Jan 1, 1991 and March 1, 2008.
Health plans and other Third Party Payors who paid all or part of the cost of one of the drugs taken by an individual not on Medicare part B between Jan 1, 1991 and March 1, 2008.
The Court will hold a “preliminary approval” hearing this Friday. If the Court grants preliminary approval to the settlement, notices will be mailed to Medicare Part B recipients and Third Party Payors, and published online and in a variety of national publications. Class members will have the opportunity to file a claim form, object to the settlement, opt out of the settlement or file an appearance with the Court. The court will eventually hold a final hearing to approve all settlement details.
This settlement is the third one announced in this AWP litigation. Iin August 2006, GlaxoSmithKline (NYSE: GSK) agreed to a nationwide $70 million settlement and in May 2007 AstraZeneca agreed to a $24 million settlement to Medicare Part B Zoladex users nationwide. After a trial in late 2006 and early 2007, the court in November 2007 ordered AstraZeneca (NYSE: AZN) and Bristol-Myers Squibb (NYSE: BMS) to pay nearly $14 million to insurance companies and consumers in Massachusetts for the companies’ roles in unfair trade practices. Those companies are appealing that ruling.
The court is expected to set a trial date for remaining claims against AstraZeneca and BMS on behalf of insurance companies and consumers outside of Massachusetts.
Consumer Reports, long a critic of drug advertising, recently introduced a new feature on its website: AdWatch. In the first episode, an Associate Editor picks apart the claims made in an ad for GlaxoSmithKline’s (NYSE:GSK) drug, Requip. The ad pitches Requip as a treatment for “Restless Legs Syndrome,” or RLS. RLS, while a real condition, has been massively overhyped by ads for drugs such as Requip. (For an excellent discussion of this, see “Giving Legs to Restless Legs: A Case Study of How the Media Helps Make People Sick” in the free journal Public Library of Science – Medicine) Requip is a drug that was originally used for Parkinson’s Disease.
Here’s Consumer Report’s very clever and thorough deconstruction of the ad:
John Mack reports on the Pharmaceutical Marketing Blog that this critique angered folks at the Restless Legs Syndrome Foundation. Guess who’s a major sponsor of this alleged consumer group? Why, GlaxoSmithKline, of course, the maker of Requip! Here’s what John Mack wrote about this today:
However, CR does have a HUGE readership that I can only dream of! As a result, its attack on Requip drew the attention of the Restless Leg Syndrome Foundation, the supposedly grassroots patient advocacy group with suspicious monetary and corporate ties to GlaxoSmithKline (GSK), the marketer of Requip (see posts cited above).
The RLS Foundation issued this clarion call to its “members”:
“We wanted to apprise everyone on our mailing list of some bad press for RLS. We want to encourage you to ‘fight back’.
“A video on consumerreports.org promises ‘relief from restless legs hype.’ The RLS Foundation is taking a tough stand against this type of bad press for RLS.
“Click here to watch this extremely sarcastic and insulting video for yourself. Then, click here to read the RLS Foundation’s response to this video.
“The RLS Foundation is calling for drastic measures to respond to this video. We aren’t concerned that they are reporting on a drug. We are concerned that they are mocking a condition that so many people live with everyday. We encourage you to respond to this advertisement immediately. If you are a subscriber of Consumer Reports, we encourage you to cancel your subscription….”
We applaud Consumer Reports for its new AdWatch feature and for examining the Requip ad. While RLS is a real condition and some people will get relief from drugs such as Requip, the shameless overmarketing of it through ads like this is enormously harmful. The purpose of drug ads is to expand the market for the advertised drug, to convince as many people as possible that they need a particular drug, even if they don’t actually need it. Since 2005, we have been calling attention to and critiquing particularly troublesome drug ads through our Bitter Pill Awards: Exposing Drug Company Manipulation of Consumers. We’re glad to be in the company of Consumer Reports in our efforts.
The Guardian today reported on GlaxoSmithKline’s (NYSE:GSK) over-the-counter weight loss drug alli (“A bitter pill for slimmers?“) and its possible introduction in Europe. PAL was featured in the article, and in particular the Bitter Pill Award we gave to GSK for introducing alli in the U.S., the “With Allies Like This, Who Needs Enemas? Award”
The article pointed out just how minimal the results from alli are:
Indeed, research found that people who took the 120mg dose of orlistat for a year lost between two and five kilograms more than people who took a dummy treatment. And while the weight might drop off quite quickly in the beginning, the drug doesn’t work for everyone and some will lose more weight than others. Research has also shown that people tend to put the weight back on when they come off the drug. This has led critics to speculate that it is the makers’ intention for people to take Alli long-term – though there is little evidence about how well the drug works in reducing weight for periods of longer than 12 months.
“The additional weight loss people have on this drug is quite minimal and this only lasts as long as they’re on it,” says Alex Sugarman-Brozan, director of the US consumer group, Prescription Access Litigation (Pal). “This isn’t the kind of drug people are supposed to take once and then stop taking. I think GlaxoSmithKlein is hoping and anticipating that people who aren’t disgusted by the side-effects will take it on an ongoing basis.”
One main question about alli is, given people’s general apparent unwillingness to make changes in lifestyle (diet and exercise), why would they make these changes as part of the alli diet plan if they weren’t willing to make those changes due to their own merits?
But some experts suggest that it is difficult enough for people to lose weight under regulated conditions with medical guidance, and are sceptical that many people buying Alli will have the motivation to reap the full benefits. Moreover, there are limited studies looking at the long-term benefits of Alli and research suggests the optimum dose of orlistat is 120mg, three times a day. So why is GlaxoSmithKlein selling something that contains only 60mg?
The company says there is little difference in the effects of the two doses – both are effective in aiding weight loss. Kaplan disagrees. He says that orlistat was never successful when it was only available on prescription. “It’s clearly a business decision. This wasn’t an efficacy decision. If the drug was efficacious it would be a blockbuster drug at 120mg, and it’s not,” he says. “Essentially, it’s a failed prescription drug from a marketing perspective. Here’s a situation where you have a drug that wasn’t a big success-a very modest success as a prescription drug-and they’re hoping, through marketing approaches and direct-to-consumer advertising, that it can be more successful as an over-the-counter drug.”
It is this that has led Pal to award GlaxoSmithKlein one of its Bitter Pill awards, “With Allies Like This, Who Needs Enemas?”
The article goes on to discuss our concern that it will be abused by people with eating disorders. The experted cited, Dr. Kaplan at Mass. General Hospital, disagrees with that concern but seems to miss the point:
Sugarman-Brozan is concerned that people with eating disorders might abuse it – but Kaplan isn’t convinced. He says the drug isn’t effective enough to be abused. In the end, he thinks the market will decide how well Alli works.
This presumes that people with eating disorders will only abuse weight loss drugs that are “effective.” Many people with eating disorders will employ strategies that are dangerous, regardless of their effectiveness, if they merely believe that they will be effective — such as binging and purging, misusing laxatives and the like. And while the modest weight loss that an overweight person would experience with alli might be dangerous additional weight loss in, say, a person with anorexia.
Let us hope that European regulators take a more skeptical look at alli than the FDA did.
Recently, we reported that Roche Pharmaceuticals (RHHBY.PK) had lost its court challenge to Australia’s ban on Direct to Consumer Advertising of over-the-counter Xenical (alli to us in the U.S., marketed here by GlaxoSmithKline (NYSE:GSK)) (Australian Court upholds ban on Xenical advertising). Now Roche reports that it expects sales of Xenical to fall, based on its inability to advertise the drug. What’s particularly telling is the quote from the story as reported on Forbes.com:
‘We feel we have done all we can and will now be considering the viability of supporting Xenical in the future,’ said managing director of Roche Products Fred Nadjarian after the judgement was announced at the end of last month.
How important, useful or effective could a drug be that cannot survive without aggressive promotion through direct-to-consumer advertising?
To paraphrase a quotation from Dr. Marcia Angell, author of The Truth About the Drug Companies, “Truly innovative drugs do not need promotion.” If Xenical were a wonder drug, it wouldn’t have to rely on TV ads.
Here’s the full item from From AFX News Limited (via Forbes.com):
Roche sees sales of weight loss drug Xenical dropping in Australia after ad ban
09.05.07, 8:20 AM ET
ZURICH (Thomson Financial) – Roche Holdings AG expects sales of its weight loss drug Xenical to fall in Australia after a federal court there banned direct advertising to consumers on concerns the drug was being sold to people who may not need it.
‘We’ve lost the ability to advertise using the brand name, which makes it very difficult to promote, so consumers will not ask for it by name in the pharmacies,’ a Roche spokeswoman in Australia told Thomson Financial News.
The pharmaceuticals group is considering its options in the wake of the court’s decision, added the spokeswoman.
‘We feel we have done all we can and will now be considering the viability of supporting Xenical in the future,’ said managing director of Roche Products Fred Nadjarian after the judgement was announced at the end of last month.
Xenical is categorised as a Schedule 3 drug, which means it is available without a prescription, but consumers should receive counselling as to its use.
Back in May, PAL awarded one of our coveted Bitter Pill Awards to GlaxoSmithKline (NYSE:GSK), for its marketing of alli, an Over-the-Counter version of Xenical, a prescription weight loss drug. In our ‘With Allies Like This, Who Needs Enemas?’ Award, we called attention in particular to the risk that making this drug available Over-the-Counter would result in its being used by people for whom it was not appropriate or even dangerous, particularly children and teenagers.
Australia wisely banned Roche Pharmaceuticals from advertising Xenical directly to consumers. (GlaxoSmithKline distributes the Over-the-Counter version of Xenical in the U.S. under a licensing agreement with Roche), particularly after Roche ran an ad during Australian Idol, a show that particularly attracts a teenage audience. Roche challenged the ban in Australian Federal Court. The Age reported on August 30, 2007 that the Court has upheld the ban.
As The Age reported, Roche had made this rather laughable argument in its court filings:
Roche challenged the advertising ban in the Federal Court, arguing members of the National Drugs and Poisons Scheduling Committee had acted against the interests of public health.
In Australia, the drug is available without a prescription, but only “Behind the Counter.” This means that a customer must specifically request it from the pharmacist, who “are legally required to measure customers body mass index and age before supplying the drug.” Even with this requirement, the Australian consumer group Choice sent a young woman with a healthy weight into a sampling of drug stores to request Xenical, and found that 24 out of 30 pharmacies dispensed it to her inappropriately.
In the U.S., the drug is only approved for use by people who are both over 18 and overweight, but there are not requirements in place to prevent pharmacies from selling it to people who are younger, or who are not overweight.
GlaxoSmithKline (NYSE:GSK) released its second quarter earnings statement on July 25, 2007. They reported that sales of over-the-counter alli hit $155 million since the drug’s launch of June 14. This means that sales of alli have already exceeeded the $150 million that GSK spent on its huge promotional campaign for the drug.
Readers of this blog know that we here at Prescription Access Litigation gave one of our coveted Bitter Pill Awards to GSK for the marketing of alli: The “With Allies Like This, Who Needs Enemas?” Award. We criticized GSK for irresponsibly marketing alli as an over-the-counter drug, removing the supervision of a physician from what used to be a prescription-only drug (known as Xenical), creating the risk that the drug will be used inappropriately and even abused, particularly by teenagers and people with eating disorders.
These earnings reports once again demonstrate that aggressive drug marketing can drive significant sales. Alli is perhaps one of the best examples of that — who would have thought that a drug that causes diarrhea, oily spotting, oily stools, flatulence with discharge, and fecal urgency could be a success? The presentation that GSK released on the earnings report states that alli had “Over 2.4 billion media impressions since approval – eclipsing recent OTC launches” and that the alli website has received 4.5 million visits with an average visit time of around 10 minutes.
Time will tell whether GSK’s sales will continue upward. No doubt there was a rush of people trying the drug because of the hype surrounding its launch, and it’s likely that side effects and disappointing results (which GSK has the gall to refer to as “treatment effects”) will discourage a good number of those who tried it from continuing. But GSK has already recouped its marketing costs, so any additional sales at this point are pure profit.
The danger is that the success of alli will encourage other drug companies to try to convert prescription-only drugs to over-the-counter status. As we said in a recent Ask Pharmie column,
For many, if not most, of the OTC drugs that are at your local pharmacy, there is no problem with them being available without a prescription: their risks or side effects are low, how to use them is clear, they treat things that patients can easily recognize, they give the consumer greater choices, etc.
But not every drug should be “self-prescribed” nor should every condition be “self-medicated.” Many diseases and conditions require a physician to diagnose them in the first place, and then to monitor them and select the right medication. For many complicated diseases, a doctor needs to occasionally change the dosage of a drug or even what drug is given, and to monitor for side effects or complications. Conditions like high cholesterol, diabetes, high blood pressure and asthma are not good candidates for making the drugs to treat them available Over-the-Counter.
Several years ago, the FDA rejected an application to make a prescription-only statin for high cholesterol available over the counter. But the approval of alli raises the question of whether the FDA will be more lenient in reviewing these applications. So-called “Rx-to-OTC switches” have long been part of the strategy used to preserve sales when brand-name drugs lose their patents (such as with Claritin and Prilosec). Hopefully in the wake of recent drug safety scandals, the FDA will be more stringent in its review of these requests. But the approval of alli doesn’t bode well for that.
Our friends at Public Citizen recently posted this YouTube video on the Paxil Pediatric settlement, and the upcoming deadline for parents or guardians of children who took Paxil to file claims to receive refunds from this $63.8 million settlement fund. (See “Deadline Approaching for Paxil Pediatric Settlement”)
Please help spread the word about this settlement and the upcoming deadline for filing claims (August 31, 2007). Visit paxilpayback.org.
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