The Price of Personalization
The idea of tailoring therapies to individual patients isn’t new. Hippocrates observed that two people could respond very differently to the same drug. Indeed, scientists have long known that variations in enzymes that help patients metabolize compounds can influence how a particular patient responds to a given medication, which may fail to have the desired effect or could cause potentially serious side effects. According to an oft-cited 2001 study, analgesics work for about 80% of users, for instance, while conventional oncology therapies are effective only for roughly one in four patients. Response rates for most other drug classes are in the 50% range. Moreover, 2.2 million Americans suffer adverse effects from drug treatment each year, and 100,000 die.
The rise of molecular medicine has seemed to promise that we could do better, and efforts toward personalizing medical therapies, primarily for treating cancer, have accelerated. For several decades researchers have known that about two-thirds of breast cancer patients have tumors with estrogen receptors, and many of those patients respond well to estrogen-blocking drugs such as tamoxifen. The widely used drug Herceptin (trastuzumab) is considered another early success story in personalized medicine. Roughly 15% to 20% of women with invasive breast cancer whose tumors have overactive HER2/neu genes are candidates for Herceptin, which blocks signals that cause abnormal cell growth and help cancer spread to other organs. Adding Herceptin to chemotherapy decreases the risk of death in women with early breast cancer by a third.
Spurred by the publication of the Human Genome Project in 2001, more and more drugs and diagnostic tests that fall under the rubric of personalized medicine have become available in the United States—from 13 in 2006 to over 100 today, according to the Personalized Medicine Coalition, an education and advocacy group whose members include pharmaceutical firms, biotechnology companies, hospitals and developers of diagnostic tools. “Personalized medicine has made significant progress in reshaping the way we think about how medicine should be practiced,” says Edward Abrahams, president of the PMC.
There are signs that drug developers concur. A 2010 survey by the Tufts Center for the Study of Drug Development estimated that as many as half of new medications in the drug industry pipeline were targeted therapies, and some firms have been particularly aggressive. One example is the Swiss pharmaceutical company Roche; according to a spokesperson, 75% of the drugs under development at Roche will have accompanying biomarker tests to be used for identifying proper candidates.
A few targeted therapies have had a profound impact on care. Gleevec (imatinib mesylate), approved in 2001 for the treatment of chronic myeloid leukemia, is often held up as one of the earliest and most successful of these drugs. Unlike conventional chemotherapy, which attacks all cells in a malignant tumor, Gleevec targets a mutation that promotes tumor growth. (Because most CML patients carry that mutation, it’s debatable whether Gleevec really qualifies as personalized medicine, a fact that underscores the lack of clear definitions in this field.) Before Gleevec, a diagnosis of CML was usually fatal, but now 95% of patients treated with the drug survive at least five years. Meanwhile, Gleevec has been approved for treating several other forms of cancer—and its price has tripled to more than $90,000 per year since it was introduced in 2001.