Carefully chosen biomarkers incorporated into clinical trials can provide critical information for drug developers. With biomarker data, researchers can more accurately determine which programs should advance, at what doses, and in which patients. More and more pharmaceutical companies are emphasizing broad biomarker plans for each drug in development in order to reap these benefits.
Pharmacodynamic markers, which indicate that the drug is having the desired effect, can be either proximal (drug target-related) or distal (disease-related). A proximal marker, such as phosphorylation of a kinase substrate, indicates whether the drug is active as expected. A distal marker, such as circulating tumor cells, provides exploratory evidence that the drug is having an effect on the disease.
Pharmacodynamic markers are especially important in early clinical trials. In first-in-human oncology trials for instance, there is not much opportunity to see clinical efficacy, but a pharmacodynamic marker can reassure study sponsors that the drug is engaging its target and is active in vivo. Furthermore, exploring the relationship between drug pharmacokinetics and pharmacodynamics is helpful for optimizing the dose levels in future trials. In some cases, there might not be a dose level that is both well-tolerated and pharmacodynamically active.
Although pharmacodynamic biomarkers can potentially provide critical information, they must be carefully chosen and implemented. Many times, the biomarkers must be assessed in a surrogate tissue, such as blood, if the target tissue is inaccessible or repeat biopsies are not feasible. Furthermore, early clinical trials are often small, and if biomarker sample collection is not prioritized or biomarker assays are not carefully qualified, then the data might not be interpretable.
A report released earlier this year by the Biotechnology Innovation Organization (BIO) called "Clinical Development Success Rates 2006-2015" states that programs that use biomarkers to select patients are three times more likely to be approved than those that do not use selection biomarkers. Knowing the group of patients that is most likely to respond is clearly an advantage. Patient selection or stratification markers ideally begin to emerge during preclinical research, but many are still exploratory in early clinical trials and cannot be truly tested until the bigger phase II or III trials. However, early trials can provide some data, perhaps through correlation with pharmacodynamic response, and they offer an excellent opportunity to fine-tune biomarker assays and sample collection protocols.
Biomarker programs can certainly add to the cost of a clinical trial, but more and more companies and organizations are realizing that a carefully designed and implemented biomarker program can help them make the right decisions.