Selling New Drugs Using Smoke and Mirrors
Worst Pills, Best Pills News article March, 2003
A former drug company executive, who also was a physician, noted while testifying before the U.S. Senate that the pharmaceutical industry is “...unique in that it can make exploitation appear a noble purpose.” The testimony was given over 40 years ago and is as true today as it was then. Capitalizing on their decades-old charade of nobility, the pharmaceutical industry is increasingly selling expensive “new” patented drugs that are chemically identical to the old drugs they replace. Remarkably, physicians prescribe them and patients pay exorbitant prices, both groups somehow believing, while being exploited, that an old drug with a new name is a therapeutic breakthrough.
How is such a sleight of hand possible? “Smoke and mirrors” aptly describes the technique. The smoke consists of phony “breakthrough” advertising, and the mirrors are represented by a chemical gimmick involving isomers.
We all know what advertising is, but what is an isomer? It is, chemically speaking, a molecule containing identical atoms to another molecule, but differently arranged: a mirror image, to be precise. Consider two isomers of a certain molecule to be like a pair of gloves — same number of fingers, just arranged differently.
So it is with many pharmaceuticals. Many exist as equal parts of a chemically identical compound that are mirror images of each other. All of the atoms in the drug molecule are the same, only their spatial orientation is different. Separating these mirror images and selling only a single mirror image as a “new” drug is a successful business scheme, not a strategy to improve public health. This may be likened to selling one glove and claiming that it is as good as or better than two.
In this article, we will look at seven pairs of drugs, one of each pair having been approved in the U.S. since the mid-1990s. The older drug of the pair is the original mix of mirror images, while the new drug is only one of the mirror images. In all seven cases, the single mirror image has never been shown to be therapeutically superior to the original mixture of mirror images. Indeed, in one case, the single mirror image was found more toxic than the mixture, and the mirror image was never marketed as a new drug.
Esomeprazole (NEXIUM) and Omeprazole (PRILOSEC)
The “new purple pill” esomeprazole is really only one of the two mirror images that make up the “old purple pill” omeprazole. Despite the fact that esomeprazole was only approved by the Food and Drug Administration (FDA) in February 2001, due to clever marketing and uncritical physicians, this drug was dispensed almost four million times in U.S. pharmacies by the end of 2001.
Esomeprazole and omeprazole are both produced by the same company, AstraZeneca Pharmaceuticals based in Wilmington, Del.
We reviewed esomeprazole in the November 2001 Worst Pills, Best Pills News and recommended that if you are currently taking omeprazole and your symptoms are being adequately controlled, there is no medical reason for you to switch to esomeprazole.
The FDA Medical Officer who evaluated the new drug application for esomeprazole wrote in no uncertain terms:
The sponsor’s [AstraZeneca] comparisons of H 40 [esomeprazole 40 milligrams] vs O 20 [omeprazole 20 milligrams] do not yield valid conclusions about the superiority of H [esomeprazole] over O [omeprazole], although these comparisons are adequate to demonstrate that H is active in the assessed indications. Therefore, the sponsor’s conclusion that H 199/18 [esomeprazole] has been shown to provide a significant clinical advance over omeprazole in the first-line treatment of patients with acid-related disorders is not supported by data (emphasis supplied by the Medical Officer in the original).
What was AstraZeneca’s motive in developing esomeprazole, a drug that has not been shown to be any better than omeprazole? Omeprazole was the largest selling prescription drug in the U.S. in 2000 with over $4 billion in retail sales that year, but was due to lose patent protection in the near future. When patent protection is lost, a manufacturer can expect a 40 to 60 percent drop in sales in a very short period of time as other drugmakers pick up production and marketing of the product. This would be a loss in the neighborhood of $2 billion for AstraZeneca, an amount that would make stockholders and mega-stockholding company executives very unhappy.
Levofloxacin (LEVAQUIN) and Ofloxacin (FLOXIN)
Levofloxacin is a fluoroquinolone antibiotic and was the 40th most frequently dispensed drug in U.S. pharmacies in 2001, accounting for almost 11.5 million prescriptions. It is one of the two mirror images of ofloxacin. Levofloxacin is the active mirror image in the ofloxacin mixture. The other has no pharmacologic activity.
At this time, there is no price advantage for patients with either drug, even though ofloxacin is no longer patent protected. However, in Canada a generic ofloxacin is sold for about one-half the price of levofloxacin — the same drug at half the price.
Both levofloxacin and ofloxacin are produced by Ortho-McNeil of Raritan, NJ. If a generic company decides to market ofloxacin, Ortho-McNeil can still sell levofloxacin as a patent-protected monopoly drug.
Levalbuterol (XOPENEX) and Albuterol (PROVENTIL, VENTOLIN)
Levalbuterol is approved by the FDA for the prevention and treatment of bronchospasm (reversible airway diseases such as asthma) and is one of the two mirror images that make up the old asthma drug albuterol.
Levalbuterol is produced by Sepracor, Inc. of Marlborough, Mass. This company has several other single mirror images under development as “new” drugs.
The editors of the highly respected Medical Letter On Drugs and Therapeutics concluded their evaluation of this drug saying, “Levalbuterol, which is available only for use with a nebulizer, appears to have no clinically significant advantage over racemic [a technical term for the mixture of the two forms of albuterol] albuterol.”
We reviewed levalbuterol in the September 1999 issue of Worst Pills, Best Pills News and listed it as a DO NOT USE drug because there is no evidence that it is any safer or more effective than albuterol. We compared the price of levalbuterol to the equivalent dosage of a generic brand of albuterol at a Washington, DC chain pharmacy. A 32-day supply of levalbuterol in a dosage of 1.25 milligrams taken three times a day costs $237.99. At the same pharmacy a 32-day supply of generic albuterol in a dosage of 2.5 milligrams given three times a day would run $37.14, one-sixth as expensive or an astonishing difference of $200.85 for an approximate one-month supply of these two drugs — about $2,400 a year.
Dexmethlyphenidate (FOCALIN) and Methylphenidate (RITALIN)
Dexmethylphenidate (FOCALIN), approved by the FDA in November 2001 for attention deficit/hyperactivity disorder (ADHD), is simply one-half of the chemically identical mixture of mirror images that makes up the 40-year-old drug methylphenidate (RITALIN).
Both dexmethylphenidate and methylphenidate are produced by Novartis Pharmaceuticals of NJ.
Dexmethylphenidate was reviewed in the August 2002 issue of Worst Pills, Best Pills News. Novartis’s “spin” to sell its old product as a new and better drug was to claim that “the duration of activity [of dexmethylphenidate] was statistically significantly longer...than methylphenidate.” Unfortunately, this strategy works with many health professionals and patients. But the FDA medical officer who reviewed Novartis’s data wasn’t fooled, saying, “This statement is misleading for several reasons.”
We agreed with the conclusion of the editors of the Medical Letter on Drugs and Therapeutics in their May 13, 2002 review of dexmethylphenidate:
There is no evidence that dexmethylphenidate (Focalin) offers an advantage over any other formulation of methylphenidate (Ritalin and others). Older drugs with better established dosages and longer safety records are preferred.
Escitalopram (LEXAPRO) and Citalopram (CELEXA)
ESCITALOPRAM (LEXAPRO) IS A FORM OF CITALOPRAM (CELEXA). THE USE OF THESE TWO DRUGS TOGETHER MAY RESULT IN AN OVERDOSE.
Escitalopram was approved by the FDA in August 2002, bringing to six the number of selective serotonin reuptake inhibitor (SSRI) antidepressants now on the U.S. market. It is the most recent member of the mirror-image marketing rage, being one-half of the mixture that constitutes citalopram. The other SSRIs currently available are fluoxetine (PROZAC, SARAFEM), fluvoxamine (LUVOX), paroxetine (PAXIL) and sertraline (ZOLOFT).
Both escitalopram and citalopram are produced by Forest Laboratories, Inc. of St. Louis.
The editors of The Medical Letter on Drugs and Therapeutics concluded in their September 30, 2002 review of the drug that:
Escitalopram (Lexapro), the active enantiomer [one of the two mirror images] of citalopram (Celexa), is effective for treatment of depression, but it has not been shown to be more effective, more rapid-acting or less likely to cause adverse effects, including sexual dysfunction, than citalopram or any other SSRI.
In our January 2003 assessment of escitalopram, we agreed with The Medical Letter’s conclusion and invoked our Seven Year Rule. We listed citalopram as a DO NOT USE FOR SEVEN YEARS drug (until October 2005) in the Companion to the 1999 edition of Worst Pills, Best Pills. We have also listed escitalopram as DO NOT USE UNTIL OCTOBER 2005 because for practical purposes, it is the same drug as citalopram and it has no therapeutic or safety advantage over citalopram or other SSRI antidepressants.
R-Fluoxetine and Fluoxetine (PROZAC)
In 1998, Eli Lilly, manufacturer of the enormously profitable SSRI antidepressant fluoxetine, announced an agreement with Sepracor, Inc., mentioned above, to develop r-fluoxetine, one of fluoxetine’s two mirror images. It was a flop and never made it to market.
R-fluoxetine was being hyped as having a more rapid onset of effect, greater efficacy for the treatment of depression, and fewer side effects than fluoxetine. Clinical trials of r-fluoxetine, however, were discontinued in October 2000 because at the highest dose tested, the compound demonstrated a small but statistically significant increase in prolongation of the QTc interval, a change in the heart’s electrical condition that can result in potentially fatal heart rhythm disturbances.
R-fluoxetine was going to be one part of Eli Lilly’s three-pronged attack to protect fluoxetine from generic competition. The company was successful in partially keeping a monopoly position for the drug by marketing Prozac Weekly and Sarafem, which is fluoxetine approved for the treatment of premenstrual dysphoric disorder (PMDD).
Many new drugs offer no health advantages to patients and are only marketed so that companies can maintain monopoly positions. These newly marketed single mirror images of old mixtures are prime examples.
Dexfenfluramine (REDUX) and Fenfluramine (PONDIMIN)
The diet drug dexfenfluramine (REDUX) was approved by the FDA in June 1996 and shortly thereafter began to register blockbuster sales as a “breakthrough” and a “cure” for obesity. This miracle of modern pharmaceutical industry hype (masquerading as innovation) was nothing more than one of the mirror images of fenfluramine (PONDIMIN), a diet drug approved in the U.S. in 1972 over the objections of the FDA Medical Officer.
Dexfenfluramine had been available in some European countries since the 1980s and was sold by Wyeth-Ayerst of Philadelphia in the U.S. It was simply an old European drug recycled in this country because the company knew it could sell a diet drug that patients and physicians thought was new.
We listed dexfenfluramine as a DO NOT USE drug in 1996 when it first came on the market because no diet pill had ever been shown to confer a health benefit for those using it (see Worst Pills, Best Pills News, July 1996).
Fenfluramine was the “fen” portion of the notorious “fen-phen” diet drug combination that severely injured so many unsuspecting patients. Dexfenfluramine and fenfluramine were removed from the market in September 1997 for causing heart valve damage and a condition of the lungs known as primary pulmonary hypertension. Clearly, dexfenfluramine was neither more nor less dangerous than fenfluramine.
The original intent of patent protection was to reward genuine intellectual creativity and true innovation. The patenting and promotion of single mirror images of old drugs fulfills neither of these criteria; indeed, it perverts the patent’s original purpose. It is nothing more than an abuse of the system for purely corporate economic goals that calls for congressional correction of the law. (Lotsa luck, the power of the pharmaceutical lobby on Capitol Hill being what it is.)
Readers please note: an excellent overview of the egregious behavior of the pharmaceutical industry was published in the December 16, 2002 issue of The New Republic. The authors, Drs. Marcia Angell and Arnold S. Relman, are both former editors of The New England Journal of Medicine, one of the most highly regarded medical journals now in publication. Angell and Relman have long been critical observers of the drug industry and this article is well worth the read.
What You Can Do
You should avoid these single mirror images of old drugs, not out of concern about their safety or effectiveness, but because they are the same as the old drugs. In the long run, they cause economic harm both to individuals and to the health care system because they have come on the market with extended monopoly protection.
In the short run, the single mirror image drugs may be sold at a discount compared to the older mixtures as an inducement to get patients and physicians to switch. Purchase wisely.
Last Updated 6/25/04