'New, Improved' Aspirin? Don't bet on it
A recent report out of Vanderbilt University (Nashville, TN) touted a university scientist's discovery of a "new, improved" variation of acetylsalicylic acid—aspirin—with all the benefits but none of the side effects of aspirin. News services picked up this story, remarking that the new compound has analgesic effects as potent as aspirin's but does not carry the potential for "dangerous side-effects."
The latest "new aspirin" hype results from work by Lawrence Marnett, a chemist at Vanderbilt University, who developed a series of compounds that irreversibly inhibit the activity of cyclooxygenase-2, an enzyme that promotes inflammation and fever, without inhibiting cyclooxygenase-1, which promotes blood clots and protects the kidneys and stomach lining. The most potent of these compounds, o-(acetoxyphenyl)hept-2-ynyl sulfide (APHS), was 60 times more reactive against cyclooxygenase-2 than aspirin was in laboratory experiments, as reported in the May 22 issue of Science.
The first thing that strikes me about this information is that "new aspirin" is an entirely different compound—a different drug with a different structure. Hence "new form of aspirin" is a misnomer. The second point involves prevention of blood clotting, a benefit of aspirin from which the drug's clinically proven cardioprotective benefits arise. Aspirin has it, but APHS (as well as other selective cyclooxygenase-2 agents) don't.
In human clinical trials aspirin has been shown to prevent colon cancer, and a recent Australian study suggests aspirin's ability to prevent angiogenesis (new blood vessel formation) might even be used to treat colon cancer. APHS acts similarly to aspirin in this regard, inhibiting blood vessel formation in cultured colon cancer cells. In fact, APHS's 60-fold higher inhibition of cyclooxygenase-2 could make the new compound even better than aspirin for fighting colon cancer. Then again, the compound has only been tested in rats, and aspirin has been around for 100 years.
It turns out that several other cyclooxygenase-2 inhibitors (notably Searle/Monsanto's celecoxib), are close to hitting the market. So the idea of a selective agent for this enzyme is not outrageous. In fact, developing such drugs is precisely how the pharmaceutical industry advances as a business and an agent for good health.
But the cavalier ease with which safe, effective (and almost always off-patent) treatments are discarded and demeaned can be bothersome.
Several reports, including one on an Internet site devoted to physicians, attributed "dangerous side-effects" to aspirin. My sources list the "most dangerous" aspirin-related adverse events as nausea (rare) and stomach bleeding (more common, but usually benign). Compare these with side effects of other "new, improved" forms of aspirin. Gastrointestinal bleeding caused by nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen and naproxen, kills about 7,600 people per year in the United States; acetaminophen can cause liver failure in modest overdoses (especially in children) and can also kill when taken with alcohol. The internet site mentioned earlier in this paragraph inaccurately blamed all 7,600 deaths due to NSAIDs to aspirin, when in fact all but a tiny fraction are attributable to non-aspirin pain relievers.
The most serious drawbacks of aspirin, from a business perspective: it is dirt-cheap, off-patent, and non-prescription. However, aspirin is one of the safest drugs on the market as measured by risk-to-benefit, deaths per million doses, serious adverse events per million doses, etc. Americans pop about 29 billion aspirins per year (11 billion of which are made by Bayer, the original patent-holder), making aspirin by far the most-used, and probably the safest analgesic.
In addition to relieving mild to moderate pain, a modest daily dose of aspirin reduces the risk of heart attack and stroke, reduces the risk of second heart attack, reduces the incidence of colon cancer and may one day even be used to treat colon cancer. Pretty good for a little white tablet costing about a penny per dose.
Still, the assault on aspirin continues. Despite its potential for serious drug interactions, acetaminophen has all but replaced aspirin as the antipyretic of choice in hospitals. Parents have been warned "never" to give aspirin to children or teenagers because of an unproven link to Reyes syndrome. And every pharmaceutical chemist has heard the apocryphal statement that "if aspirin were discovered today it would not get through FDA regs." Given the enormous evidence of aspirin's safety and efficacy, this seems more an indictment of our drug-approval process than of aspirin.
No, we probably don't need another "new aspirin." We do need new, safe, effective painkillers in our product pipelines. Perhaps even more critical is our need, as pharmaceutical professionals and consumers, for reliable information on what's important in our industry and what's not. So my response to developers of unproven drugs that address merely academic shortcomings of the most popular pharmaceutical in history: Take two and see me in the morning.
Comments? Email me at adepalma@pharmaceuticalonline.com.
Angelo DePalma
Managing Editor, Pharmaceutical Online