Monday, November 21, 2005

The Development and Marketing of Zegerid - And How AstraZeneca Didn't "Want To Do a Study in Sick People"

The San Diego Union-Tribune has weighed in with its own investigative reporting on "me-too drugs." We previously posted on me-too drugs here.

The story focuses on the marketing of Zegerid by San Diego pharmaceutical company Santarus. Zegerid is simply a combination of omeprazole, a generic proton pump inhibitor (PPI), i.e., a drug used to decrease stomach acid, and sodium bicarbonate, a simple chemical used for years as an antacid. Because this combination is treated by the US Food and Drug Administration (FDA) as a new drug, even it simply combines an old and an ancient generic drug, Santarus can market it as a brand-name product. Although 42 doses of over-the counter omeperazole costs about $25 at retail, Santurus is selling 30 doses of Zegerid for about $140. Santurus is marketing the combination product, in the form of a powder that is dissolved in water, as the "first and only immediate release oral PPI."

Clinically, the advantages of an "immediate release oral PPI" are not obvious. Extended release PPIs are used (as are H2-blockers, which are available generically and over the counter) to treat indigestion, gastro-esophageal reflux disease (GERD), and peptic ulcer disease. Drugs that work for a fairly long time are useful to prevent symptoms throughout the day (or night). If one needs immediate release, simple antacids work quite well.

The story of Zegerid's development is instructive. The combination of omeperazole and sodium bicarbonate was developed by Jeffrey Phillips, a pharmacologist in the Department of Surgery at the University of Missouri. A comatose patient in the intensive care unit (ICU) had developed a bleeding ulcer despite intravenous therapy with an H2-blocker. Phillips tried to figure out how to administer a PPI to her, but the extended release coating on Prilosec (omeprazole) clogged the patient's nasogastric tube. But Phillips found that by dissolving the Prilosec in water and adding sodium bicarbonate, he produced a solution he could give through the tube, and the patient's bleeding stopped.

Phillips tried to interest some large drug companies in developing the combination for use in critical care, but without success. Finally, Santarus acquired the rights to it for $1 million.

Although pharmaceutical companies tout their high prices as necessary to support cutting edge research to develop life-saving drugs, Santarus paid relatively little on research on Zegerid ($44 million), compared to the amount it has already spent on administration and marketing, $48 million in 2004 to hire a 400 person sales team.

Dr. John Santa, of the Oregon Health and Science University Center for Evidence-Based Policy, commented,

When a company can get a patent for turning an existing drug into a powder and use clever marketing and tiny differences in study results to sell it, the tail is wagging the dog.
In fact, most of the marketing for Zegerid turns on a single article [ Castell, D., Bagin, R., Goldlust, B., Major, J. & Hepburn, B. (2005)Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease.Alimentary Pharmacology & Therapeutics 21 (12), 1467-1474. ] that showed the combination produced a higher (more normal gastric pH) than did a PPI alone. However, the study was too small to determine if that different in test results translated to any improvement in symptoms or other outcomes. Thus Santa also commented,

This is a perfect example of an issue that advertisers can promote that in fact is not meaningful for patients and doctors. We need to ask why we should pay for something that costs twice as much, or 10 times as much, when there is only a tiny difference - and the difference doesn't translate into less pain or something that matters.
Finally, Phillips' pursuit of a company willing to develop his drug combination to treat critically ill patients produced an important insight into the minds of those who now lead large health care organizations. Phillips approached AstraZeneca, the maker of Prilosec (omeprazole). According to the Union-Tribune, "the company didn't want to do a study involving ICU patients, fearing that deaths and adverse events would tarnish Prilosec's safety record." According to Phillips, one "bigwig" said,
We don't want to do a study in sick people.
Phillips responded,
Dude, these patients are dying because they are bleeding from these ulcers.
The bigwig replied,

Well, what if they die while on the drug.
Phillips' last riposte was,

What if they die and it's a Friday? No one thinks Friday made them die.
In summary, this showed pharma leadership who seemed utterly uninterested in helping really sick patients, and utterly ignorant of the basic premises of clinical research. Such leadership, of course, is not likely to produce products that really benefit the patients who need the most help, and hence seems unworthy of the huge compensation that top pharma leaders now seem to command. What sort of health care are we going to have when "bigwigs" don't want to deal with "sick people?"

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