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Advancing the Development and Clinical Use of Biomarkers

Posted on June 21st, 2016 by in Pharma R&D

Biomarker-based patient selection for clinical trials

Biomarker-based patient selection for clinical trials, a hallmark of precision medicine, is gaining traction. On Monday June 6, a team of researchers reported at the American Society of Clinical Oncology annual meeting and in an online paper in JAMA Oncology that biomarker selection results in better outcomes in Phase l trials. The same team previously showed the benefits of biomarker selection in Phase 2 trials and in trials of US Food and Drug Administration-approved anticancer drugs.

For the Phase l study, Maria Schwaederle, PharmD and colleagues from the University of California San Diego’s Center for Personalized Cancer Therapy examined response rate and progression-free survival in a meta-analysis of 346 clinical trials of targeted agents involving a total of 13,203 patients. By comparing results of trials that used a precision medicine approach (58 treatment arms) with those that did not (293), they sought to determine whether using a biomarker to select patients improved efficacy.

They found that in the precision medicine arms, more than 30% of patients responded to treatment compared with only 4.9% of those enrolled in the non-personalized arms. Patients selected using biomarkers also had a longer progression-free survival (median, 5.7 months) before their disease worsened, compared with 2.95 months for other patients.

When they did a subgroup analysis of the 234 treatment arms testing targeted therapies, the researchers found that assigning treatments based on biomarkers led to response rates of 13.1% compared with 5.1 for those that did not.

They concluded that “a biomarker-based selection of patients, even in the Phase 1 setting, is associated with significantly better outcomes,” whereas “treating patients with targeted agents without a biomarker selection strategy produces very low [response rates] in the early clinical trials setting.”

Taken together with the results of the earlier studies, the findings suggest that biomarkers may be used effectively to improve outcomes not only in later stages of drug discovery and development, but also early on. Their use not only helps patients by identifying those most likely to respond to treatment—it also helps pharmaceutical R&D by enabling researchers to identify and address any safety-related issues before moving a candidate drug to the next stage of development. This is good news for all concerned.

What’s ahead for biomarkers? The FDA says it is committed to “advancing the development of new targeted drug therapies by enhancing the science of biomarkers.” The agency has a Biomarker Qualification Program in place to support the development of biomarkers for drug development and facilitate the integration of biomarkers into the regulatory review process and in regulatory decision making (i.e., pharmacovigilance). Biomarkers can also serve as a surrogate endpoint for those seeking accelerated approval of a new drug.

A March 2016 report, Biomarker Tests for Molecularly Targeted Therapies: Key to Unlocking Precision Medicine, from the US National Academy of Medicine contains recommendations to further advance the development and appropriate clinical use of biomarkers. Most of the recommendations will impact researchers in all sectors. These include:

  • The development of “consistent and coordinated evidentiary standards and study design approaches, including rapid learning systems that simultaneously accommodate the various types of decisions (including clinical, regulatory, coverage/reimbursement, and guideline recommendations).”
  • On the regulatory front, “primary (and follow-on) biomarker test review and approval with detailed test labeling requirements” and “a defined process for coordinated updates of biomarker test and drug labels.”
  • Support from the Patient-Centered Outcomes Research Institute and the US National Institutes of Health, as well as other funding groups, for “the assessment of the clinical utility of biomarker tests for molecularly targeted therapies using rapid learning approaches.”

Other recommendations include developing a national repository of biomarker tests for molecularly targeted therapies; improving specimen handling; developing/updating clinical practice guidelines to include biomarker tests; health coverage/reimbursement; equal access; and good physician-patient communication about the tests and their results.

An article by Garret Fitzgerald of the University of Pennsylvania’s Institute for Translational Medicine and Therapeutics, published June 15 in Science Translational Medicine highlights some of the key points of the report that will impact clinicians and patients. In particular, he notes the call for labeling of biomarker tests associated with specific molecularly targeted therapies—and the capability of updating them regularly, something that will impact manufacturers, too.

All of this argues for organizations to invest resources now in systems that enable early identification of relevant biomarkers, the pairing of those biomarkers with targeted therapies for the best possible outcomes, and the ability to track those biomarkers for regulatory purposes throughout the development process and post-market.


All opinions shared in this post are the author’s own.

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