By: Issam Zineh, PharmD, MPH, FCP, FCCP
A key area of new drug development lies in the field of targeted therapies, sometimes called “personalized medicines,” which are drugs tailored to the genetic makeup of individual patients. These drugs are called targeted therapy because health care professionals can use clinical test results from a patient to select a specific drug that has a higher likelihood of being effective for that particular person. FDA is working with a wide range of scientists and scientific organizations to help advance the fundamental biomedical science necessary to support this growing field.
The successful development of targeted therapies requires biomarkers – measureable indicators in the body such as proteins or DNA changes – to identify patients at risk of worsening disease and those with a high likelihood of treatment benefit or experiencing treatment failure. Having biomarkers that can help health care professionals diagnose disease, identify the stage of a disease, or predict patient response to treatment also has the potential to make drug development more efficient. For example, biomarkers can be used to identify patients to enroll in clinical trials, which can make trials smaller or shorter because the drug’s effect is measured only in people who are likely to respond. There are now several drugs on the market that were developed with a biomarker-based diagnostic test that can be used in the clinic to identify patients. Examples include Xalkori (crizotinib) and Tarceva (erlotinib), used to treat forms of lung cancer, and Zelboraf (vemurafenib), used to treat certain types of melanoma (skin cancer).
Biomarkers can be helpful in the development of new therapies, whether or not they are targeted therapies. For example, identifying reliable biomarkers that can substitute for clinical “endpoints” can speed up drug development. This is because showing that a drug has a meaningful effect on a biomarker is generally easier and takes less time than showing that the drug has positive effect on the way a patient feels, functions, or survives. The availability of established biomarkers may also attract greater interest and investment in a drug’s development and can help minimize financial losses with earlier identification of poor performing drugs.
The ability to identify useful biomarkers depends on how well scientists understand the disease for which they are seeking treatment. In some disease areas, such as cancer and infectious diseases, we have made great progress in understanding disease processes and the ways to affect these processes with drug therapy. In less well-developed areas, FDA is working to promote biomarker-based strategies in drug development. For example, we currently have a process for “qualifying” biomarkers for regulatory purposes.
Recently, FDA teamed with the Brookings Institution’s Engelberg Center for Health Care Reform to host a public workshop to help advance biomarker science for therapeutic product development. Discussions helped to identify and to propose solutions for scientific challenges for biomarker applications in early and late phase clinical trials for new drugs, as well as best practices for successful biomarker-based programs. Some opportunities highlighted in the discussion include:
- Clear standards about the evidence needed to support use of biomarkers;
- Infrastructure and policies that promote development of tests used to identify patients for trials and in the clinic, particularly tests designed to evaluate many biomarkers at one time;
- New models and networks for clinical trials that will accelerate both biomarker and new product development; and,
- Methods to assess treatment effects in small populations identified by sequencing technologies.
Public input from this workshop will be used to help FDA in its decision making and communications about biomarkers. As part of its mandate under the Prescription Drug User Fee Act Reauthorization of 2012, FDA is committed to advancing the development and use of biomarkers in medical product development. The public workshop was a significant step in helping us fulfill this obligation. Finding ways to advance the identification and use of biomarkers in drug discovery and development also has been a focus of the House Energy & Commerce Committee’s recent 21st Century Cures initiative. We look forward to continued efforts to advance biomarkers, which will help bring important new therapies to patients in need.
Issam Zineh, PharmD, MPH, FCP, FCCP, is Director, Office of Clinical Pharmacology, Office of Translational Sciences, in FDA’s Center for Drug Evaluation and Research