BOSTON — Proteomics researchers in academia and industry wishing to play a role in the emerging “theranostics” market should consider partnering with drug or diagnostic companies early in the pre-clinical stages of product development, scientists said during a session at the Biomarker Pipeline conference, held here this week.
The goal of this kind of research — which aims at jointly developing and marketing companion diagnostic and therapeutic products — is to help physicians select the right patients for treatment and track treatment progression, the scientists said.
Their statements were prescient: The US Food and Drug Administration is expected to release a draft guidance on companion diagnostic/therapeutic products later this year. However, it is unclear whether the guidance will include information on protein biomarkers, or if it will address only DNA-based biomarkers.
Calls to Robert Becker, a director in the FDA’s center for devices and radiological health who was present at the conference, were not returned by deadline.
Speaking during a workshop entitled “Biomarkers: A Business Perspective,” Brian Edmunds, a manager of new technologies at Eli Lilly, said that theranostics should be an integrated process for all pharmaceuticals.
“We all want disease biomarkers,” said Edmunds. “We want to know who’s predisposed, how far along a patient is with a disease, who are the correct patients to select for therapy, who are the responders to drug therapy.”
Edmunds outlined a number of things to consider when taking on a diagnostic partner to accompany drug development from the stages of hypothesis through discovery, assay development, preclinical validation, and clinical validation.
During the discovery phase, especially if the test is proteomics-based, scientists must carefully consider issues of sample collection and experimental design, Edmunds said. Scientists must also consider bioinformatics issues so that the test stands up statistically, especially if the test is based on a combination of biomarkers.
Once a biomarker candidate has been identified, scientists should consider the feasibility of the biomarker, how to implement it, and how to sell it, Edmunds said.
A timeline is an important factor to consider in the development of a biomarker, Edmunds pointed out.
“You have to look at timelines so that you can get a co-launch [of the biomarker and the drug],” he said. “And you have to look at market readiness — how much pre-sell will you need to do? And implementation — how will you sell it?”
Scientists should consider throughout the biomarker-development process why the biomarker is important, Edmunds said. For example, in the case of sepsis, it is known that the longer it takes to diagnose a patient, the greater the chance the patient will be misdiagnosed. Currently, however, there is no way to measure how long a patient has had the condition, and the process of diagnosis is usually a long one that involves exclusion of other conditions.
A biomarker for sepsis would be important for quick diagnosis, and for diagnosing the stage of the condition. Moreover, only about 30 percent of patients respond to sepsis drugs, so a biomarker could also be useful in determining which patients would respond to treatment, Edmunds said.
“You have to make sure [the biomarker] always supports the clinical product’s goals,” said David Deems, vice president of system development and operations at Predicant Biosciences, a San Francisco-based company that develops proteomics-based diagnostics. “You have to tap into the right opinion leaders, the right physicians.”
During his talk on “Making the Transistion from R&D to Product Commercialization,” Deems emphasized that biomarker developers must have a strategic team to brainstorm up front what is likely to happen down the road.
“Keep in mind that ultimately, spending the time up front in defining a strategy will facilitate decision making and accelerate the path to development,” said Deems.
Deems pointed out that a new technology — for example, a panel of protein biomarkers based on SELDI technology — is not necessarily harder to pass through the FDA if testing is done properly and it is shown that there is a clear patient benefit.
To illustrate his point, Deems cited two cases: In one case, a recommendation to limit the exposure of healthy tissue to radiation did not pass through an FDA review board because of a “lack of published data” on the benefits, despite the fact that the recommendation is based on an old technology and seemed to make common sense.
In a second case, a new genomic test based on new technology was cleared by the FDA “with flying colors” because the testing was done properly, and a clear patient benefit was demonstrated.
FDA’s Becker agreed with Deems.
“In terms of which regulatory route a device takes [and consequently, how hard the road is to approval], the thing that drives the device is not so much the newness of the technology as the risk associated with the application of that device,” Becker said during a panel discussion on biomarkers at the conference.
Tests that help to select therapy for patients, such as the EGFR test for various cancers and the HercepTest for breast cancer, are typically placed in approval Class III because of the risk these tests have for patients, Becker noted. A new test that is safe and effective and that has relatively low risk could be put through a less arduous de novo 510K Class II process, he pointed out.
In responding to Becker’s comments, Shawn Ritchie, a senior scientist at Canadian metabolomics company Phenomenome Discoveries, pointed out that early detection markers may carry high risks and are not always welcomed.
“With early detection markers, you have to ask, ‘Is this something that you really want?’” Ritchie said.
Physicians often don’t want an early diagnostic test if there is no intervention for the disease at that early stage, Ritchie noted. For example, a test that predicts breast cancer in four or five years is of questionable value when the next intervention step is mastectomy, and the risk of misdiagnosing somebody could mean unnecessary surgery.
“A lot of physicians say, ‘I don’t want that burden’ [of having an early diagnosis test],” said Ritchie. “Especially if there’s no intervention, that knowledge could be a huge stress. There’s a large ethical component to early diagnosis.”