Many More Patients Will Be Needed for Trials of the Future

BOSTON—Targeted anticancer drugs such as trastuzumab (Herceptin) targeting HER-2 and imatinib mesylate (Gleevec) targeting Bcr-Abl represent the potential of genome-based medicine, but the future may not be as close as it seems, according to pharmaceutical executives who spoke at the 2001 Drug Discovery Technology Conference.

They predicted an increase in the number of drugs to be tested as a result of research into the human genome and a decrease in the time needed for the early stages of drug development. Clinical trials take years, however, and thousands of patients will be needed for some of the studies that are envisioned. As large numbers of new targeted drugs reach the clinical trial stage, it could create a medical logjam.

Klaus Lindpaintner, MD, MPH, vice president and head of genetics for Roche Genetics, F. Hoffmann-La Roche AG, Basel, Switzerland, called clinical trials an unavoidable "bottleneck" through which new drugs must pass. "We need clinical data to get drugs approved. It’s the meat that we need to put on that scaffold of the genome," he said.

Participating in a press briefing on the effect of genomics on pharmaceutical research and development, Dr. Lindpaintner said that "thousands of patients and thousands of controls" are essential for complex studies that consider how genes, mutations, and environmental factors affect illnesses and therapies.

"When it comes to clinical research, you can’t funnel patients through quickly. They take time. There isn’t any magical shortcut," he said. He called acquisition of sufficiently large patient cohorts for clinical studies the major stumbling point in drug development today.

Importance of Markers

George M. Milne, Jr., PhD, senior vice president, Pfizer, Inc., Groton, Connecticut, predicted that finding genomic markers to identify and monitor patients will become increasingly important in clinical trials. He forecast that early phases of future investigations would focus on using markers to identify which patients might benefit from a therapy. "I think it will have an increasing impact on the early definition of clinical efficacy and the selection of doses, both of which are tremendous challenges in drug development," he said.

Dr. Lindpaintner said that Roche has already started collecting DNA from all participants in its clinical trials, and the consensus among the executives was that DNA testing would eventually become as standard as hemoglobin counts.

Markers identified through genomics could be used to give drugs that fail phase III trials another chance, Dr. Lindpaintner said. "If you have a bimodal distribution of good responders and bad responders, and your good-responder group is relatively small, you might want to retest that drug, giving it only to those identified as being likely to respond," he said.

The main obstacle might not be biology, but persuading a large drug company to invest money in post-phase III trials targeting small groups of patients with markers that suggest they would be responders.

By this point, the company has spent $500 million or so on developing the drug, said Werner Kroll, PhD, program director for pharmacogenomics, Bayer AG, New Haven. "I can tell you from personal experience that it is very difficult—once people have burnt their fingers and it has cost them a lot of money—to get them to go back and study a drug from scratch with a different viewpoint," he said.