New genetically engineered drugs promise targeted patient care
Recent decisions by two Food & Drug Administration advisory committees to recommend approval of Enbrel (etanercept, Immunex) and Herceptin (trastuzumab, Genentech Inc.) signal milestones in the development of genetically engineered drugs.
Etanercept uses a revolutionary way of relieving the symptoms of rheumatoid arthritis (RA). It targets and neutralizes tumor necrosis factor (TNF), an immune system protein associated with RA, from attracting inflammatory cytokines to the affected joints. According to the manufacturer, the drug, which comes as a powder for injection, also seems to cause far fewer side effects than existing medications for RA.
In the case of trastuzumab, it has been engineered for the 30% of patients who carry a defective gene called Her-2/neu. The defective gene is related to EGFr: a growth-message relay switch that's hyperactive in many patients with aggressive breast cancer. Adding trastuzumab to standard chemotherapy has produced better results than standard cancer therapy alone. In fact, the trastuzumabcontaining regimen has more than doubled the chances of dramatically shrinking breast cancer tumors.
Trastuzumab is the first in a wave of genetically engineered treatments that promise a gene-based attack on cancer without the side effects of chemotherapy. The drug uses monoclonal antibodies, which are clones of human antibodies that target a single protein. "It heralds a new age in how we are going to treat cancer with better understanding and targeted therapies," said Dennis Slamon, M.D., of the Jonsson Cancer Center at the University of California, Los Angeles, whose genetic research led to the development of trastuzumab.
In a parallel development in the genetics diagnostics field, Oncogene Science Diagnostics, Cambridge, Mass., a subsidiary of OSI Pharmaceuticals, has developed a standardized serum diagnostic test for the Her-2/neu protein. The test could provide oncologists with a tool for determining therapeutic dose and for monitoring patient response to therapy. Gary Frashier, OSI's chairman and CEO, said the test is "the first in a series of gene-targeted diagnostic tests that we believe will be integral to the effective use of the new generation of gene-targeted cancer drugs under development throughout the pharmaceutical industry." Working with Bayer Corp. Business Group, Diagnostics, OSI plans to submit an application to the FDA later this year for clearance to market an in vitro serum diagnostic test for Her-2/neu.
Diagnostic tests for all kinds of gene-targeted drugs are going to be an important part of medicine and pharmacy in the 21 st century.
Even before receiving final FDA clearance for marketing, trastuzumab is being described as a forerunner to the more advanced genetically engineered drugs that will emerge from the genetic or genomic revolution. Everyone agrees that the revolution, which began in the early 1990s, now heralds a new golden age in biology. Industry sources agree that gene-targeted and other genetically engineered therapeutics in development today will come to market in the next seven to 10 years. These new medicines will be revolutionary because some of them will actually eradicate the genetic problems that cause disease.
While no part of health care will remain untouched, the genomic revolution will have its most dramatic effect on the pharmaceutical industry, which has moved quickly to get up to speed on genomic technology. Suddenly, every major pharmaceutical company is getting involved with biotechnology and investing heavily in genomics.
Genomics is the study of all the genes of an organism, including their sequences, structures, regulation, interaction, and products. The science is changing the face of the pharmaceutical industry because major companies are now transforming themselves from businesses that develop drugs based on medicinal chemistry to organizations focused on biology and genetics. …