Litigation, Knock Offs and Nepotism : Welcome to the U.S. Pharmaceutical Industry

[McCamy Taylor]

Beware! This journal is almost as big as the greed of Big Pharm in America.

Government intervention will undermine quality and patient choice.

From Why the New Congress Should Not Fix Drug Prices A Heritage Foundation statement from 2006

http://www.heritage.org/Research/HealthCare/wm1270.cfm




Case I: Skelaxin or Why Create a New Drug When You Can Slap a New Patent on an Old Medication?

My husband came home with a prescription for the muscle relaxant, Skelaxin (generic metaxalone). This in itself is not remarkable. His job keeps him physically active, and he works out regularly. Occasionally, he pulls a muscle. He surprised me, however, when he complained about the cost of the medication. It totaled almost $300 for a month’s supply.

I went to medical school back in the early 1980s, and Skelaxin/metaxalone was an old drug even then. There had to be some mistake. Any medication that ancient must be available in a generic.

I turned to my old pal, Google. No, there was no mistake. A pharmaceutical company named King Pharmaceuticals had applied for----and gotten---and exclusive patent to manufacture and sell name brand Skelaxin from 2002 through 2021.

http://www.drugpatentwatch.com/premium/preview/detail/index.php?searchtype=alpha&category=Tradename&searchstring=SKELAXIN

But….but….this drug is almost as old as I am. I realize that the rules changed during the Bush administration, but could drug companies really just waltz in and slap a new patent on some old grandfathered in medication like aspirin or digoxin?

Apparently, the answer was yes. If the drug company could discover a side effect or idiosyncrasy or problem with the medication that might change the way that doctors had to prescribe. Now, I am not talking about a new use for the medication. Skelaxin was always a muscle relaxant. However, if you read this FDA document, you will discover that a researcher “discovered” that if you take Skelaxin with a fatty meal, you absorb more of it.

http://www.fda.gov/ohrms/DOCKETS/dailys/04/mar04/031904/04p-0140-cp00001-01-vol1.pdf

Ordinarily, this is the stuff of warning boxes. You know

Do not take this medication with grapefruit juice, since this may increase serum concentrations and increase its effect.

However, King Pharmaceuticals persuaded someone at the FDA that this new information made Skelaxin a new drug. All they had to do was rephrase that warning to say

Do take this medication with food so that you get even higher serum concentrations (and more potential for side effects).

Any generic drug manufacturer that wanted to produce and sell Skelaxin had to do its own studies on bioavailability---something that generic manufacturers are not in the business of doing. For one thing, it would raise prices. For another, it is redundant. And since when is there a patent on side effects and warnings? For the record, there are a whole bunch of drugs whose bioavailability is affected by the foods we eat. These range from blood thinners to medicines for mental illness. If every manufacturer was given an extra 20 year patent for “discovering” something that should have been disclosed to the FDA as part of the original testing, no drug would ever become available as a generic.

As a result of this sleight of hand, King Pharmaceuticals was able to sell Skelaxin for the inflated price of almost $300 a month from 2002 to the present. In 2008, Skelaxin was ranked 54 in overall sales and brought in $500,000,000.00. Metaxalone is a niche product, since it causes less drowsiness than some other the other muscle relaxants on the market (most of the others have a cheap generic), meaning that there are probably people---especially elderly people---with recurrent back pain who can not do without the product. And instead of paying $50 for a bottle, they are paying close to $300 a bottle.

This situation is not scheduled to change until 2012. King finally gave up defending its indefensible phony patent and agreed to let a competitor, Core Pharmaceutical start selling a generic metaxalone in 2012.

http://www.fdanews.com/newsletter/article?articleId=103111&issueId=11213

In the meantime, King has raked in $3 billion from this drug alone, money that they can now use to lobby against health care reform. Sweet deal for them. A waste of health care dollars for the nation.

II. Case II: Humibid LA or How Adams Laboratory Also Slapped a Patent on an Old Medication

Guafenesin is the active ingredient in Robitussin. It is used to loosen up phlegm. People with diseases like asthma and chronic bronchitis, some of the biggest causes of morbity and mortality in the U.S., depend upon it. The med is derived from a Native American remedy and the FDA cleared it for use as a drug in 1952---

http://en.wikipedia.org/wiki/Guaifenesin

1952! That makes it even older than me. Plus, I prescribed generic sustained release guafenesin all through the 1990s. So, why did the FDA give Abbot Labs an exclusive patent to sustained release guafenesin, the most useful form for people with chronic lung disease, in 2002? A patent good through 2020. That is eighteen years of exclusive profits from a medication that was over half a century old. Why, in 2007, did they attempt to suppress Abbot’s competition again with this action?

http://www.topix.com/forum/drug/robitussin/T60QJGJTGBLKV2VJB

WASHINGTON (Reuters) - The U.S. Food and Drug Administration on Friday ordered an end to the manufacturing and distribution of certain cough and cold medicines containing the expectorant guaifenesin that are sold without the agency's approval.
The products, made by about 20 drugmakers and mostly available by prescription, are time-released and are used to clear mucus from the lungs. But they never underwent the FDA's formal clearance process, the agency said.
Only two such medicines -- Mucinex and Humibid made by Adams Respiratory Therapeutics Inc. and available over the counter -- have U.S. approval.

Unlike Skelaxin, sustained release guafenesin is absolutely essential for the health of millions of Americans. So, when Abbot jacked up the price and when it stopped producing the pediatric formulation of the product and when it tried to minimize sales of Humibid to give its newer, competing patent drug Mucinex (that you see all over TV) a boost in sales, consumers protested.

http://www.psha-inc.com/guai-support/sf/InternationalGuai-SupportGroupNetworkFDAProtestStrategies.htm

Linked from the above site, here is a powerful letter to the FDA which describes the way that drug companies, like Abbot, make money in America.

http://www.psha-inc.com/guai-support/sf/DownloadCopyOfGGResponseToFDAUnapprovedDrugsCompliancePolicyGuide.htm

When FDA removed pediatric Humibid from the market last October, they left a very vulnerable section of the population with no access to a very necessary drug. There is no sugar free, single ingredient, sustained-release guaifenesin, suitable for children, left on the market. Pediatric Humibid sprinkles were the drug of choice. Now there is NO CHOICE. Our children deserve better treatment. The medical community, the pharmaceutical Industry, the drug manufacturing industry and the American public do NOT agree with removing this drug from the market.

It is many years too late to be demanding millions of dollars in fees to "approve" these old, safe drugs, and hundreds of others. All that this will accomplish is the financial destruction of many small drug companies which provide the competition that keeps prices down. It may also remove some of these drugs from the market entirely. This will leave the poor with a lot fewer choices of affordable medication. In the case of guaifenesin, there is no other choice to be made. If Adams Labs fails financially, Mucinex will disappear, leaving the consumer with no form of sustained-release guaifenesin. They would have a difficult time trying to sell the manufacturing rights, as their patent is under litigation at this time.

snip

Adams Labs had a total monopoly on sustained release guaifenesin for many years. The patent on Humibid expired a few years ago. Due to recent law changes, they could not extend it. So they created a NEW guaifenesin tablet, using old bi-layer technology, which is the legal property of others, gave their product a new name and created a whole new way to EXTEND A PATENT THAT HAD RUN OUT without having to seek a law change. This action violates all intent of law as it pertains to the deliberate prevention or hindrance of generic forms of a patented drug being made available to the consumer in a timely manner.

snip

THIS is an entirely different situation from one where a company has spent millions of dollars on research and development, THUS there is no justification for a 'compensatory' monopoly. Mucinex is just old sustained/immediate release, generic and non-patentable Guaifenesin. Adams Labs sought a way to regain total control of the market that they had enjoyed for many years without competition. By using legal loopholes, and deception, they succeeded. Guaifenesin is not a new drug. It has existed in medical use for many hundreds of years. It is beyond all patentability.

How did Abbott get away with this flagrant abuse of patent law, even going so far as to put children with asthma and cystic fibrosis at risk in their quest for more profits? Maybe the answer can be found in their political contributions reports. From 2006, Sourcewatch
http://www.sourcewatch.org/index.php?title=Abbott_Laboratories

In 2006 Abbott Laboratories spent $2,260,000 for lobbying. $880,000 went to outside lobbying firms with the remainder being spent using in-house lobbyists
Snip
Abbott Laboratories gave $566,474 to federal candidates in the 05/06 election period through its political action committee - 18% going to Democrats and 82% to Republicans

III. Case III: How the FDA Banned Cheap Generics of Quinine and Ergot to Boost Sales of GlaxoSmithKline’s Immitrex and Requip.

I first began to suspect that the FDA cared more about Big Pharm than about the US people back in March 2007. The feds did something very unusual. They tried to ban the sales of two time tested grandfathered in medications, quinine which was used for leg cramps and ergotamines for migraine headaches. The timing of this move was suspicious, considering the fact that GlaxoSmithKline had been conducting aggressive direct to patient marketing campaigns of the two drugs that people deprived of their quinine and ergots would have to switch to----Requip for the leg cramps at close to $300 a months and Immitrex for migraines at $4 a pill, $25 per nasal spray dose. These ads had appeared in television in the few months leading up to this FDA move---almost as if the drug company and the FDA had coordinated their actions.

You can read my old Kos Diary here for more details and links. While the two old, cheap generics have side effects, so do GSK’s products .

http://www.dailykos.com/story/2007/3/2/14243/36440

Case IV: How Hoescht Got the FDA to Ban Its Own Seldane So That It Could Extend Its Seldane Patent as “Allegra”

In the 1990s, drug company Hoescht was about to lose one of its big cash cows. The only non-sedating antihistamine on the market at the time, Seldane, was about to go generic. That meant that cheaper versions would be available.

So, what did Hoescht do? Look at page 18 of this Power Point Presentation on “International Patenting Strategies” given last year.

pharmexcil.com/data/uploads/Dr.Kausalya.ppt

Allegra extended the patent life of the original compound.

Note that every medication has side effects. For some time, people had known that if you took Seldane with certain other drugs, particularly erythromycin, it could (rarely) cause a serious heart arrhythmia. Lots of meds have interactions and they are allowed to remain on the market, even if there are other products that do the same thing which do not have these interactions. Physicians and pharmacists are supposed to be smart enough to know how to prescribe safely----that is why these are prescription drugs and not over the counter.

However, Hoescht had acquired a slightly modified version of its own Seldane which it called Allegra, another nonsedating antihistamine which did not have the drug interaction. If you read between the lines of this New York Times article, you will discover that Allegra’s sales were not picking up. The way I see it, Hoescht had expected doctors to switch their Seldane patients to their new drug, which they promoted as safer. However, patients and doctors knew that generic Seldane was on the horizon. A manufacturer of generic drugs even won approval to start marketing generic Seldane. So, people hesitated to switch.

Until, in an unprecedented move, the FDA acted to ban Seldane.

http://query.nytimes.com/gst/fullpage.html?res=9804E2D61338F937A25752C0A961958260

Unfortunately for Hoescht, their twice a day Allegra was about to encounter every drug’s worst nightmare, a once a day alternative, Claritin.

Case V: If Cardiac Side Effects Mean an Automatic FDA Ban, How Come GlaxoSmithKline’s Avandia is Still On the Market Despite Its Association with Heart Attacks?

Note that Seldane was linked to 40 reports of heart arrhythmia and eight deaths. The NYT article (and the FDA) does not describe how many of these were due to prescribing errors by physicians as opposed to the toxicity of the drug used by itself. Consider the case of theophylline toxicity. Theophylline is used to treat severe asthma. From time to time, a physician will prescribe an asthmatic patient who is taking this medication another drug which is known to increase theophylline levels in the blood. This can cause serious side effects and even death. However, when this happens, the FDA does not take Theo-Dur off the market. The prescribing physician is blamed.

Also note that the same FDA which is supposed to be so concerned about patient safety still allows GlaxoSmithKline to manufacture and sell the diabetes medication Avandia despite studies linking it to heart attacks.

http://www.medicinenet.com/script/main/art.asp?articlekey=81240

Which makes you wonder, when the FDA considers the toxicity of medications like Avandia and ergotamines and quinine, are they thinking about the toxic side effects they can have on you or me, or are they more concerned about potential toxic effects on the pocketbook of GlaxoSmithKline?

The news got even worse for Avandia last November with advance reporting of this article from the Archives of Internal Medicine detailing another study of the drug which confirmed the link to heart attack and showed that it posed an even higher risk of heart failure than Actos, a similar diabetes medication.

http://health.usnews.com/articles/health/healthday/2008/11/24/avandias-heart-risk-higher-than-others-in-its-class.html

Note that the FDA’s response to the reports of heart attacks with this drug was to demand 1) a black box warning and 2) more studies of all diabetic drugs. None of the articles about the medication suggest that errors in writing prescriptions---i.e. doctors or pharmacists giving this drug to the wrong people or with the wrong other medication---contributed to its problems. The drug itself seems to be the problem. However, Avandia is number 94 on that list I linked above. It brings in $378,000,000.00 a year. That makes it much too important for the health of GSK for the FDA to ban.

Case VI. Baycol Was a Symptom of the Flawed Pharmaceutical Industry

Remember Baycol, Bayer A.G’s attempt to break into the lucrative world of statin type cholesterol lowering drugs?

During post-marketing surveillance, 52 deaths were reported in patients using cerivastatin, mainly from rhabdomyolysis and its resultant renal failure.<1> Risks were higher in patients using fibrates, mainly gemfibrozil (Lopid), and in patients using the high (0.8 mg/day) dose of cerivastatin. Bayer A.G. added contraindication about the concomitant use of cerivastatin and gemfibrozil to the package 18 months after the drug interaction was found.<2> Frequency of deadly incidents of rhabdomyolysis with cerivastatin was 16 to 80 times higher than with other statins.<3> Another 385 nonfatal cases of rhabdomyolysis were reported. This put the risk of this (rare) complication at 5-10 times that of the other statins. Cerivastatin also induced myopathy in a dose-dependent manner when administrated as monotherapy, but that was revealed only after producer of cerivastatin was sued and unpublished company documents were opened.

http://en.wikipedia.org/wiki/Cerivastatin

You might be tempted to think that Baycol was designed specifically to kill people. I promise you, it was not. The current insane drug patent system rewards pharmaceutical companies for taking a competitor’s big product, rearranging a molecule here or there, doing a few studies at which point they can announce Hey, we have our own statin! Where is our hundred million dollars?

All the statins were originally derived from compounds extracted from microorganisms. You can get the same effect with Chinese Red Yeast Extract

http://www.mayoclinic.com/health/red-yeast-rice/NS_patient-redyeast

Indeed. Merck’s Mevacor is nothing but a purified version of the Chinese Red Yeast Extract---with a patent, of course.

While Big Pharm warns that health reform will stifle their urges to create new and better drugs, in fact, Big Pharm is not interested in new and better. They want the same thing their competitor has. So, as you can see from this wiki entry, they invested way too much money tinkering with Red Yeast Extract.

http://en.wikipedia.org/wiki/Statin

If you play around with Mother Nature at random like that, you know that sooner or later someone is going to stumble across the active molecule which causes the medication’s toxicity, and their modification of that molecule is going to make its effect even worse. It was bound to happen to someone. The makers of Lescol managed to decrease the potency of their version of the parent drug---leading them to cut deals for cheap, bulk sales to HMOs as a way to increase their market shares. Unethical but it won’t kill anyone right away. The makers of Baycol managed to make their statin even more poisonous.

So, in addition to being wasteful, the practice of Me too! patent medications is also dangerous.

I could go on and on like this. The current pharmaceutical industry design rewards CEOs with eight figure salaries for quick profits made through political contributions and litigation rather than actual medical research. As a result, consumers pay too much for an array of drugs that is too narrow---and we can not rely upon our own FDA to protect us from the snake oil salesmen, because nowadays, the FDA works for Big Pharm---

Case VII. Almost Forgot...

Oh, my! Did I write about the greed of Big Pharm and forget to mention the Medicare Drug Price Gouging Extravaganza that Bush and the Republicans handed them? I would not want anyone to think that the FDA is to blame for everything that ails the American Pharmaceutical Industry. The American Pharmaceutical Industry is responsible for everything that ails it. Why bother creating new drugs when you can just raise the prices of the ones who already make? As soon as the drug companies acquired the ability to charge Medicare patients as much as they wanted for their drugs under the new Medicare Prescription Drug Benefit, the price of the top drugs used by the elderly began to rise. Ordinarily, if the federal government was bulk buying that much of any one medication, the price would fall. Also, competition would keep prices down, correct? That was what W. claimed when he threatened to veto Democrats' attempt to insert a bargaining agreement into the law the next year.

http://www.npr.org/templates/story/story.php?storyId=6498336

Currently, the law expressly forbids the government to do that. President Bush says he would veto the change, because, he says, competition among private insurers lowers drug prices more effectively than government negotiation could.

Except that there has been no competition. The drug companies have raised their prices in lock step, almost as if they are colluding. This report shows that the drugs most commonly prescribed under Medicare have risen in price at 2.5 times the rate of inflation. That does not just happen. Someone---or some group of people---make it happen.

http://healthpolicyandmarket.blogspot.com/2008/03/drug-prices-rise-7-for-drugs-most.html

Meanwhile, the federal government, which should have been regulating the drug companies, has been looking for ways to keep others from regulating drug companies. Case in point, a last minute present from Bush to Big Pharm aimed at shutting down state investigations of companies that promote off label uses. You know, test a product for schizophrenia in adults and then tell doctors to use it for depression and ADD in children. The FDA, which would not let us have quinine or ergot, because they said that their use for leg cramps and headaches had not been studied, is now going to let drug companies start promoting their patented formulations for anything, everything ---

http://www.mcclatchydc.com/homepage/story/61113.html

---without performing studies to document that the medications are effective for the new problem or that they are safe.

Pardon me, but didn't the FDA just contradict itself? The only way to make any sense out of the actions of that agency over the last eight years is to assume that there is a poster on the wall of FDA headquarters which reads

If Big Pharm Wants It, Then It Is Medically Sound

[HysteryDiagnosis]

1. Kicked and recommended 5,000 times. Excellent work on

explaining how big pharma tries to help lower healthcare costs while ignoring their own interests.

[Oceansaway]

2. ...K&R...n/t...

[D-Lee]

3. Thank you! A real eye-opener on something else wrong with the FDA

Magnificent work.

[jmowreader]

4. Beautiful! Makes me wish for a "recommend 10x over" button!

One of the big things President Obama really needs to do is to create a corps of freelance patent examiners, people who have the brains to know when something doesn't deserve the mantle of patent protection.