The use of biomarkers early in the process sets up the hypothesis and potentially advances the timeline for later trials.
If biomarker data is to be available for regulatory submission, use of biomarkers in Phase IIa/IIb is critical. Companies
currently using biomarkers in Phase IIa/IIb–Phase III are better positioned to advance than their counterparts. Thus, this
approach becomes a key portfolio decision step.
Various companies are organizing their biomarker efforts in different ways:
Novartis is one industry leader in its embrace of biomarker technology. Four years ago, the company instituted a safety assessment
biomarker program at the preclinical stage of compound development to reduce failures in clinical trials. Two years ago, Novartis
made an R&D commitment to implement biomarkers from discovery through Phase IV, putting this global line function in place
under the responsibility of Jacky Vonderscher, PhD, vice president and global head of biomarker development.
In the past two years, the company hired new personnel in key executive positions to ensure biomarker plans and programs are
consistently in place to impact the attrition rate of compounds early, accelerate proof-of-concept trials, and define clinical
safety and efficacy biomarkers early in the process.
At Eli Lilly, "The key goal is to improve technical success for our molecules in clinical development," explains Eiry Roberts, MD, vice
president, project/program medical. This process translates into an active reduction in uncertainty around key technical risk
factors (for example, toxicology, clinical dose selection, exposure/response, and so forth), and shifts the attrition curve
to earlier in the process across the portfolio.
Biomarker strategies in support of new compounds help to optimize the portfolio, not the individual molecule. At present,
the focus is on early-stage development, when discovery teams are asked to develop biomarker tools to assess drug activity,
safety, and efficacy in the clinic.
"As compounds move from discovery to validation, the biomarker strategy is implemented," explains Brian Edmonds, PhD, principal
research scientist at Lilly. "As each compound passes the go/no-go decision, the biomarker strategy is brought forward on
a case-by-case basis for compounds that receive a 'go.'"
Bristol-Myers Squibb initially created separate groups for clinical biomarker technologies but found the model to be ineffective. One year ago,
the company fully integrated clinical biomarker personnel into the drug development process, making them part of therapeutic-area
teams and enabling them to gain a robust understanding of the area by consistently working with the same group.
Biomarker strategies for each compound are developed early in the drug development process. The clinical discovery group (from
Phase I to proof of concept) is responsible for implementing the clinical biomarker strategy. These changes are beginning
to show signs of success.
"The key is to gain therapeutic area consensus around what we are/are not doing. By putting biomarkers into the routine development
processes, organizational consensus on priorities and goals are gained, as is consistency in decision making," says Nicholas
Dracopoli, PhD, vice president for clinical discovery technology.
Pfizer global research and development organizes its biomarker effort vertically, according to Stephen Williams, PhD, MD, the company's executive director and worldwide
head of global clinical technology platforms, who supports all therapeutic areas. The company has developed biomarker best
practices in research and development, which cover the plan, properties/use, tolerability of risk, performance, and minimally
acceptable criteria for performance.