The backlash after the withdrawal of the arthritis drug Vioxx is in full swing.
Critics of the pharmaceutical industry and the Food and Drug Administration's (FDA) effort to modernize the drug development process are using the drug's link to a higher risk for heart attacks to raise questions about the FDA's safety review process and the value of new medicines overall. They say longer clinical trials should be required and newer, targeted, "smart" drugs like Vioxx should be tested against their cheaper, blunter ancestors before they are allowed on market.
Lost Lives, Higher Drug Prices
That mindset, however, will slow medical progress to a crawl by leading to larger, longer, and ever more expensive clinical trials designed to identify increasingly rare adverse effects. Adding more layers of onerous regulations to the FDA approval process will actually hurt patients: It will forestall the distribution of drugs that are safe for the vast majority of users, and it will keep new products off the market far longer. That will cause a direct cost in lost lives and higher drug prices.
Vioxx's critics have forgotten that patients using older drugs are often exposed to worse side effects and receive fewer benefits than with the newer drugs. Arthritis sufferers are especially at risk because using non steroidal anti-inflammatory drugs (NSAIDs) for long-term pain management exposes patients to a high risk of serious gastrointestinal problems, possibly leading to bleeding ulcers and even, in some cases, death.
The politics of global drug withdrawals and longer drug development times is a scientific step backward in an era when both common sense and science demonstrate that, as an article in the New England Journal of Medicine noted, "different patients respond in different ways to the same medication" (see "Drug Therapy: Pharmacogenomics Drug Disposition, Drug Targets, and Side Effects," Evans, W. E. and McLeod, H. L., New England Journal of Medicine 348: 538-549, February 6, 2003, http://content.nejm.org/cgi/content/full/348/6/538).
That observation is borne out by the new science of pharmacogenomics, which demonstrates how drugs are metabolized differently in different groups of patients based on genetic variations.
Critics Remain Unconvinced
Nonetheless, critics still insist most drugs produced by industry and approved by the FDA are "me-too" drugs, copycats of each other that are not even better, or possibly even worse than, generic NSAIDs already on market, such as aspirin, ibuprofen, and naproxen. But research has shown that in many cases only one drug will work for a particular group of arthritis sufferers. Vioxx is no exception. Many people who took Vioxx had found Celebrex didn't work for them, and they couldn't take ibuprofen or aspirin because they were at high risk for gastrointestinal problems or allergic to those medications.
In fact, the Washington Post recently chronicled how patients formerly on Vioxx are struggling to find substitutes that allow them the same level of pain relief and functionality ("Withdrawal Symptoms: Patients, Doctors Explore Alternatives For Arthritis Relief Very Carefully," Washington Post, November 23, 2004). One patient, a 58-year-old osteoarthritis sufferer for whom other treatments were less effective, was even quoted in the article as saying, "I'm concerned [about risks], ... [b]ut you [also] have to talk about quality of life. [If Vioxx was still available] I probably would've stayed on it."
Before there was Vioxx, there was aspirin. And now, of course, aspirin is used widely to prevent a second stroke or heart attack. But medical researchers have evidence that so-called "aspirin resistance" is much more common than formerly believed--perhaps as many as 50 percent of all high-risk patients taking aspirin therapy develop this condition. "Resistance" in this case means a patient's cells do not respond by producing the blood-thinning platelets needed to fight off another stroke or heart attack. However, researchers are working to develop an inexpensive blood test by which to detect this resistance and determine if the aspirin dosage should be changed or if an alternative medicine should be prescribed to help prevent clotting.
Moving Toward Personalized Medicine
This is exactly the kind of personalized medicine we should be able to offer all patients, and the FDA and pharmaceutical companies could use this approach, moving to match medicines to the people who can benefit from them the most, instead of pulling drugs off the market altogether.
The cutting edge of this drive toward personalized medicine is in identifying the unique genetic pathways that trigger disease, finding the subtle genetic differences that explain how we metabolize drugs, and discovering which genes cause us to reject or react badly to various medicines. As scientists develop what are called pharmacogenomic tools to tailor drugs to our genetic profile, doctors will be increasingly able to give the right drug to the right patient at the right time.
This isn't science fiction. Genaissance Pharmaceuticals has already identified 29 biomarkers that "were found to have statistically significant associations with clinical response" to each of four different statin drugs, the company announced in a report of clinical study results last year. As this research progresses, the report maintained, doctors will be able to "optimize [statin] therapy based on the genetics of different patient populations."
Dr. Stephen Liggett, a professor of medicine at the University of Cincinnati and advisor to Genaissance Pharmaceuticals, has already helped the company develop tests to identify genetic variations that affect an individual's response to medications for asthma and congestive heart failure. Using this personalized approach, Liggett says, "we have been able to take people who were miserable or near death and bring them back to a normal life."
Pharmacogenomics will revolutionize drug development as well. Biotech and drug firms will be able to use genetic screens to identify the right group of people for whom prospective compounds work best. That will enable safer and faster testing using smaller groups of patients earlier in the development process. Faster and more efficient drug development will mean lower drug prices for new drugs.
Combining targeted medicines with targeted blood tests would ensure that each drug prescribed is the right "medical match" for each patient, virtually eliminating the kind of adverse effects that now emerge only years after a drug is first approved. Pharmacogenomics will help ameliorate safety concerns and increase public confidence in both the FDA and the industry.
Backlash Threatens Progress
The backlash against Vioxx could set the pharmacogenomics movement back by years, as regulators throw needless hurdles in the face of advancing technology. Before this happens, policymakers, researchers, and the FDA will have to redouble their efforts to improve and increase the use of pharmacogenomics in drug development and explain to the public why excessive caution toward new drugs will cost more lives than it will save.
After all, delaying drug development or reverting back to older, one-size-fits-all medicines is no substitute for a new generation of treatments tailored to our genetic profiles. Nothing else will make tomorrow's drugs any safer or affordable for patients.