I read your book, "Medicine Science and Merck". In it, you talk about how you tried to re-direct how drug discovery was approached at Merk when you first arrived. I recently attended a talk about computer programs that have been designed to predict new drugs by looking at currently used drugs and making modifications. It made me realize that in your career you must have really seen the field of drug discovery change a lot. What do you think have been the biggest changes to the field of drug discovery and where do you think the future will bring us? Thank you. I enjoyed your book and your talk at the AACC meeting in July.
St. Louis, MO
P. Roy Vagelos
Drug discovery in the past was based on understanding the pathogenesis of a disease (the cause) and determining a method (drug) that would block the development of the disease. Thus coronary heart disease was thought to be due to accumulation of plaques containing cholesterol in the arteries that would block the flow of blood. Lowering blood cholesterol was the focus of a research project. Slowing the formation of cholesterol by the liver was the target for drug discovery. Drugs were discovered that did this. They were called "statins" and they revolutionized the treatment of heart disease. At the present time drug discovery is based on understanding the function of genes that are involved in the development of a disease. Functional genomics, that is understanding the function of each of the genes, will determine which ones are involved in disease. Then the proteins coded by those genes will be targets for drug discovery. This new approach will be very productive and lead to exciting new drugs for diseases that have no current therapy, but also better drugs for diseases that currently have some form of treatment that is not optimal.
Dr. Vagelos- You certainly have had an interesting career! Can you elaborate on how the first statins were discovered and developed?
P. Roy Vagelos
The statins are the drugs currently used by most doctors to treat coronary heart disease because they reduce the ability of the body to make cholesterol and thereby reduce the incidence of heart attacks. They were initially discovered by focusing on an enzyme that is critical for the liver in making cholesterol. That enzyme is blocked by this class of drugs, the statins. The first statin that was effective and safe enough to be marketed was lovastatin (Mevacor at Merck). Lovastatin was the product of a soil microorganism. Once it was isolated and purified, it was tested in animals to be demonstrate the reduction in blood cholesterol. Then it went into clinical trials where it was shown to be safe and effective in reducing blood cholesterol and low density lipoprotein cholesterol (the bad cholesterol). Lovastatin was launched in the US in 1987. Simvastatin, (Zocor of Merck) was studied in patients who had coronary heart disease and high blood cholesterol. About 4,400 patients were studied in a double blind study where half the patients received the drug and the other half received a dummy pill (placebo). At the end of 5 years, the patients who had received the drug were found to have had a reduction in mortality from any cause of about 30%, a reduction in death from heart attacks by about 43%, a reduction in need for coronary surgery, and a reduction strokes. These results essentially transformed the treatment of heart disease. Since the publication of the results of these studies which were augmented by many other studies showing similar results, many patients throughout the world are treated with one of the statins.