Promise and Peril
The Herceptin story offers an encouraging epilogue about the development of small-market drugs. Annual sales of the drug began modestly at $188 million in 1999. But sales have climbed steadily to about $346 million in 2001, and Genentech has deftly marketed the drug and expanded its possible uses. Originally approved for patients with the Her-2 marker who had developed metastatic breast cancer and had failed to respond to all other forms of chemotherapy, Herceptin is being tested as supplementary therapy following surgery for breast cancer and in cases of ovarian and lung cancer in which Her-2 is overexpressed.Rituxan, an anticancer drug developed by IDEC Pharmaceuticals and marketed by Genentech, has followed a similar pattern. The FDA approved the drug in 1997 for non-Hodgkin’s lymphoma, a cancer that affects certain immune-system cells with a surface marker called CD-20. That marker allows for a targeted attack on malignant cells. Genomic analysis is identifying gene expression patterns that correlate with the disease’s progression; such analysis will ultimately affect treatment decisions. From initial sales of $162.6 million in 1998, its first full year on the market, Rituxan racked up sales of $818.7 million in 2001 and was well on its way to becoming a billion-dollar drug with expanded use by the end of 2002. The cells targeted in non-Hodgkin’s lymphoma may play a role in other diseases, such as chronic lymphocytic leukemia and rheumatoid arthritis, so the market may well extend even further.
So the pioneering drugs of personalized medicine convey messages of both caution and promise: Caution about the effect targeted biomarkers can have on a patient population, as well as the way the reaction of those patients can in turn influence the testing of drug candidates and the public’s perception of a company. Promise that a patient population can be identified and treated with a targeted drug that offers greater efficacy, as well as that nonresponders may be spared the ravages of toxic, ineffective treatments. And promise, too, that even a drug targeted to specific biomarkers can have economically bright prospects. The trick will be to capitalize on the promise without leaving too many disenfranchised patients behind.
As bumpy and fitful as was Herceptin’s journey to market, it serves as an inspiration to latter-day practitioners of personalized medicine. “I’m sure Genentech was having to wrestle with the decision of, If only 20 to 25 percent of the population responds, how are we going to compete?’” says Millennium’s Ginsburg. “But somebody had to be first, and I think it’s great that they did it.”
Despite the economic challenges and societal issues associated with personalized medicine, its role in the future of medical care seems all but assured. Not only is personalized medicine going to happen, argues Stephen Laderman, manager of the molecular diagnostics department at Agilent Labs’ Life Science Technologies Laboratory, in Palo Alto, CA, but it is going to happen soon, in part because more and more patients are learning to demand whatever knowledge will empower their decisions about disease treatment. As patients learn more about their options and researchers learn more about the molecular specifics of their patients’ diseases, personalized medicine may still be a bitter pill for many to swallow, but it will be one well worth taking as an antidote to the ravages of disease.