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Me-too Mythology


Robert Goldberg, Ph.D.
August 19, 2004

How many medicines are "enough" to treat a single disease like cancer, depression, or AIDS?

Many critics of the pharmaceutical and biotechnology industries insist – without any supporting evidence – that just a couple of drugs in each therapeutic class for most diseases would be sufficient. They believe that companies producing anything beyond the first or second drug in a class are just making a rank attempt to keep profits flowing as older drugs go off-patent, without adding any real gains to public health.

These critics want the FDA to force drug manufacturers to conduct head to head clinical trials comparing new drugs to medicines already on market for the same condition before they can be approved. Critics call the compounds that would be weeded out by this process "me-too" drugs, i.e. virtual clones of existing drugs that the public would be just as well off without.

The critics, however, pay scant attention to what we already know about the genetic basis of disease, to say nothing of the cumulative experience of decades worth of drug development in both the public and private sectors.

Psychiatrists treating patients for depression routinely juggle medications to find one that works; they may even combine two or more drugs to alleviate severe depression. Patient compliance is also a very serious issue; lithium and other older anti-depressants have significantly more side-effects than newer drugs, meaning that patients would rather go without medication than continue to take older drugs. According to Dr. Frederick Goodwin, the former director of the National Institute of Mental Health, and one of the world's leading experts on mental illness and medicines, "practicing physicians know that the large number of SSRIs (selective serotonin re-uptake inhibitors) has been a boon for patients, because they do respond very differently to different drugs in that class. Some, sadly, still don't respond to the many drugs we do have."

Drugs also have multiple uses for multiple conditions; sometimes a drug that is the third or fourth in its class may also have enormous value for other conditions. The most commonly used class of migraine drugs, triptans, doesn’t work for 20-30% of migraine sufferers. As a result, researchers have turned to other classes of drugs – anti-convulsants (Topamax and Depakote), heart disease drugs (beta-blockers), and even Botox to help treat and prevent migraines.

Finally, genetics teaches us that very slight genetic differences between patients can create enormous differences in how some patients respond to drug treatment. For all the chatter about how every cholesterol and blood pressure drug is alike, recent genetic tests show that individuals have very different responses to different drugs. Gleevec, a breakthrough chemotherapy drug for some leukemia patients, is next to useless for other patients whose disease has small genetic mutations. As a result, researchers and pharmaceutical companies are rushing to tweak Gleevec's molecular structure to make it more versatile. Thus the next, or next several, Gleevec-like compounds may be only be very slightly different from its predecessor – but would also be substantially more effective. According to the critics, these Gleevec-like molecules will fit the definition of a me-too drug (virtually the same molecule, same class) and yet will be a real breakthrough for a whole new group of patients still praying for a cure and using old-style chemotherapy.

Even the drugs most industry critics love to hate, the COX-2 inhibitors Celebrex and Vioxx, have excited researchers for their potential to prevent colorectal cancers – and other uses may hover just around the corner as researchers learn more about the role COX-2 enzymes play in oncogenesis.

In other words, the best scientific studies, the best experts and the genetics shaping the next generation of personalized medicine demonstrate that very similar drugs work and effect different people quite differently. Cutting out "me-too" drugs would not only hurt patients taking those drugs now, but it would rob scientists of the ability to find new uses for those same medications in the future.

Still, isn't testing new drugs against old drugs a good approach that will help patients and doctors find the best therapies? Sure – and once the drug is on market competitors often have powerful financial incentives (witness the jousting for market share among statin drugs, for instance) to truly demonstrate to consumers, insurers and government programs that their medicines reduce health costs and improve well-being.

Clinical issues aside, testing every new drug against every old drug in the same therapeutic class would amount to financial suicide for pharmaceutical companies. Randomized clinical trials are extremely expensive and time consuming. They are also clumsy because they can only test one drug and one illness at a time. In the real world, people have multiple conditions and take a combination of drugs, and physicians frequently use drugs "off-patent", i.e. for other uses than which they were originally approved. Barring companies from marketing products until the results of multiple head-to-head trials for each dose and each condition are available would slow research to a literal crawl and would kill patients in the meanwhile.

The current FDA standard for drug approval - establishing safety and then proving efficacy versus a placebo - isn't perfect, but it does move the ball forward.

And that is the real goal of science – not limiting research to "breakthroughs" but advancing medical science through small incremental gains, the kind of gains made when drugs reach market that are just a bit better or better tolerated than older ones.

This not to say that breakthroughs don't happen in the system now. They do. Industry has made enormous strides in treating AIDS, cancer, and heart disease within the last twenty years. Other innovative drugs are in the pipeline, and more will come as scientists learn how to identify the best drug targets in the recently decoded human genome.

But, in the meantime, the public needs to understand that drug discovery is risky and unpredictable work. Half of all biotech drugs seem to work as expected until about two-thirds of the way through the development process. And then – several years and hundreds of millions of dollars later – they flounder in late stage clinical trials.

Trying to pick the winners and loser in this process is self-defeating because researchers can never predict what will constitute a "breakthrough" drug until they have already invested years of research and enormous financial capital studying it. And many companies are working on the same kind of drug around the same time, racing to be the first on the market. If companies couldn't hope to recoup their financial investment until they had proven that their drug candidate was superior to a competitor's medication they wouldn't bother with the R&D in the first place.

Still think that everyone should be happy with just a few drugs in every class?

What if you were bi-polar and were one of the 30 percent of the population whose disease still resists treatment despite the availability of lithium, Depakote and a variety of anti-convulsants? What if your daughter were bulimic but needed a drug to stabilize her behavior so that she could take in enough water and food to survive, and the only drug that might work was the sixth and most recent anti-psychotic drug on the market?

Could you imagine yourself or your family waiting an extra year or two, or three, until new drugs were tested in head-to-head clinical studies before your doctor could prescribe them – if at all?

For those patients and people like them there is no such thing as a "me-too" drug. There is just one word to describe those drugs.

Hope.

Robert Goldberg is Director of the Center for Medical Progress at the Manhattan Institute for Policy Research.

 
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