What goes into researching and developing a cancer drug and what is required for FDA approval? We sat down with Moshe Talpaz, M.D., associate director of translational research at the U-M Comprehensive Cancer Center, for a closer look at the FDA approval process.

What is the first part of the process to develop a new drug?

The pre-clinical process is quite elaborate. Academic medical centers like U-M have the role of discovering what governs a disease, to discover the mutation that drives an illness like cancer. We first focus on the biology to show the full sequence of events in the body. We develop various laboratory approaches to demonstrate that shutting off the abnormal protein kills the cancer cell.

Drug companies then get involved to develop what is called a lead compound. Medicinal chemists study many different molecules to identify one that has the characteristics of potentially becoming a drug. A lead compound then becomes the subject for extensive testing on animals to determine whether it has adequate pharmacologic behavior and a good toxicology profile. In other words, that it works safely in the body.

When does research begin with actual patients?

The pre-clinical studies are followed by Phase I testing in humans to find the maximum tolerated dose. We start with very low doses, of course, to check for toxicity. If patients can tolerate it, we try a higher dose. We end up with a safe dose to recommend for use in a Phase II study.

Phase II involves more extensive testing and is where we demonstrate whether the compound is effective and which tumors respond to it. We want to see what percentage of patients with a certain disease respond to the compound, although the number of patients in this phase may not be sufficient for definitive assessment.

Phase III is a randomized study of large groups of patients that compares the potential drug to the current standard of care. If the compound reaches a significant goal, which is acceptable to the FDA, the FDA approves it as a new drug and it is given a trade name.