Taking advantage of a shift in pharmacogenomics strategies that has been evolving in recent years, a group of innovators has emerged to focus on genotyping patients before they are prescribed a treatment.
Fueling this group is the interest in theranostics, which has continued to build and accelerate as the Food and Drug Administration promised to issue draft guidelines for the products by the end of the year.
In a recent study outlining the ways in which pharmacogenomic technologies are incorporated into the laboratory and the clinic, a team led by Andrew Webster of the University of York examined the strategies, constraints, and drivers affecting the technologies’ entry into the healthcare marketplace.
The researchers counted about 30 small biotechnology shops and a similar number of large pharmaceutical companies as the major entities pursuing pharmacogenomics technologies. The study also identified a “third group” comprising diagnostic firms and healthcare providers, including public health agencies, collaborating with smaller firms, who Webster said are most interested in improving the safety and efficacy of existing drugs, as well as developing drug-test combinations.
In the study, which appears in a special pharmacogenomics supplement published this month in Nature Reviews, Webster and colleagues contend that most large pharmaceutical companies approach pharmacogenomics as a way to ensure the safety and efficacy of drugs in development, and to discover drugs both for particular genotypes and for all variants. Smaller biotechs and genomics firms often perform a supporting role in this model, while also concentrating on improving the safety and efficacy of already approved drugs.
This two-pronged strategy may favor the tack employed by firms concentrating on upstream drugs — those currently in development — according to Webster. “I think in that sense it’s reached a sort of innovation plateau at the moment for smaller firms who’re going to have to tie themselves into fairly small niches in networks with large corporations,” said Webster “If they can do it upstream in [drug development], that’s likely to be a more secure hand for them to play than downstream in improving safety of licensed drugs and efficacy of licensed drugs,” because that option allows healthcare providers and government agencies to restrict the focus of research to particular licensed drugs, he said.
To be sure, the commercial opportunities through this type of engagement with public health agencies are “quite limited” in terms of profit, partly because of the constraints on public programs, said Webster. “But smaller companies might find a niche and be happy with that, within that context,” he said.
The number of new companies has experienced a slowdown in growth since 2000, both in small- and medium-size pharmacogenomics companies and in the number of their collaborations, Webster and colleagues wrote.
Innovadigm Oncology, of Research Triangle Park, NC, is among the companies aiming at tests for drugs in development. Its strategy is to “use biomarkers and technology platforms to define patient populations” most likely to respond to a specific cancer drug, said CEO and cofounder Michael Stocum(read complete interview on p.6). The approach — Stocum calls it “targeted clinical development” — involves enrolling patients in a drug trial based on “applying biomarkers in pathways that are related to tumors,” as well as commonplace clinical parameters, such as prior treatment regimens.
“This hasn’t been done frequently, bringing companion products together to the market,” said Innovadigm’s Stocum. The US Food and Drug Association, the private sector, and academia are all gradually catching on to new technologies and their pharmacogenomic possibilities, he said, allowing a chance to put in place an intelligent scheme to speed up the regulatory process and product development. He said the FDA is taking steps to ensure that this begins “moving in that direction.”
“What is interesting about this strategy is that it in part is a response to the FDA accepting that such biomarkers might make for speedier (and so less expensive) clinical trials, and thereby open the door for more CRO activity than might have been the case,” Webster, the author of the Nature Reviews paper, wrote in an e-mail. Innovadigm’s strategy differs from that of companies focusing on downstream drugs, he added.
For Webster, useful regulatory equilibrium might “take some time to reach.” However, the authors expect regulators to encourage pharmacogenomics testing before a drug is prescribed when a drug has a narrow therapeutic index and is efficacious in perhaps 30 percent of the population.
Another difficulty is finding a confluence of business needs between the pharmaceutical and diagnostic industries, said Stocum. Whereas diagnostics generate lower profit margins than therapeutics, and revenue is “based on volume and the ownership of platforms in the clinical laboratories,” pharma companies traditionally cash in on high-margin products.
Challenges also exist among healthcare providers. Webster wrote that clinicians’ concerns about pharmacogenomics centered around the “use and practicality” of the technologies “in specific clinical contexts,” and the relatively weak evidence supporting the technologies’ introduction. Even if available, strong evidence would still remain only one of “several biological and environmental factors” used in distinguishing between therapeutic options, Webster wrote.
In the face of these challenges, the introduction of pre-prescription genetic testing for drug response in regard to existing drugs “is much less certain,” although investment by diagnostic firms and healthcare providers would help.
“Companies like Roche and Pfizer and Glaxo — the ones that have spent the most time and effort looking into this sort of thing — they’re the ones that have to convince the regulators as to what this particular [theranostic] hybrid animal is,” Webster told Pharmacogenomics Reporter.