By Turna Ray
In recent years, the few drug developers in attendance at the annual Personalized Medicine Conference in Boston generally held the view that pharmacogenomics wasn't ready for prime time as a drug development strategy, but a survey of the drug industry presented at the same meeting this year showed that pharma is slowly changing its tune.
The report by the Tufts Center for the Study of Drug Development, presented at the conference hosted by the Partners HealthCare Center for Personalized Genetic Medicine last week, showed that around 80 percent of pharmaceutical firms are working with academic medical centers, research institutions, and healthcare practitioners on personalized medicine projects.
The Tufts researchers began the survey last year, when they interviewed 20 employees at 13 drug firms to get a reading on where the industry stood in terms of the application of genetic strategies to drug development. Then, this year, Tufts CSDD surveyed 16 respondents at drug companies to gather more quantitative data.
According to Christopher-Paul Milne, the study's lead author and associate director at the Tufts CSDD, the researchers spoke to 21 companies in total. Milne described half of the firms as being among the top 20 pharma companies, and the other half as falling into the top 20 biotech category.
The overall takeaway of Tufts' report paints an optimistic picture about the increasing adoption of personalized medicine strategies by drug firms. Companies surveyed by Tufts said that between 12 percent and 50 percent of their current clinical development pipelines involve personalized medicines.
Furthermore, the report suggests that between 2006 and 2010, drug companies increased their investment in personalized medicine by more than 70 percent on average. In the next four years, these firms are expected to increase their investment in the discipline by more than 50 percent.
This shift from the blockbuster mindset to focusing on treatments for smaller subpopulations didn't happen overnight. In fact, it took significant shifts in the corporate culture of pharma and biotech to begin investing in personalized medicine.
"In terms of the cultural change that personalized medicine engendered among companies, the respondents said that internal organizational and R&D paradigm changes were necessary sometimes despite resistance by senior management that were resistant to change," Milne told PGx Reporter.
The shift toward genomically targeted drug development began as "companies incorporated a personalized medicine capacity that was separate unto itself and interacted with research groups in the therapeutic areas or installed a personalized medicine unit within each therapeutic area," Milne added.
All companies in the Tufts study said they were using biomarkers or targeted therapies in the discovery phase of the drug-development process. However, the report notes that "an associated biomarker is not a requirement for compounds to move into clinical development." Tufts also identified some companies that require personalized medicine endpoints for all trials, which they use to make decisions about how to advance the compound in their pipelines.
"Most [companies] generally agreed that biomarkers make it easier to make go/no-go decisions and that personalized medicine is a natural trajectory for the direction that advances in science and medicine were taking drug R&D," Milne said. However, the survey also revealed that "there is some debate as to whether personalized medicine is helping to streamline R&D because of the scientific challenges that remain in interpreting and acting upon pharmacogenetic data."
For the time being, it seems that biomarkers are predominantly used by drug companies to learn more about the investigational agent being developed, rather than inform "prescribing or monitoring requirements on the label."
The US Food and Drug Administration has urged industry to shift the drug development paradigm to more genomically guided strategies. In this regard, the agency has been increasingly updating labeling of previously approved drugs with genomic data. The agency also launched the Voluntary Exploratory Data Submissions program a few years ago, through which industry can discuss early genomic data with FDA reviewers without regulatory repercussions.
Among the companies surveyed by Tufts, 69 percent have so far submitted data to the VXDS program. In addition, the study found that approximately 50 percent of clinical trials now involve the collection of DNA samples from study participants.
With the help of the VXDS program, more drug firms are coming to the agency early in the development of their drugs to discuss Rx/Dx combination strategies. Donna Roscoe, a scientific reviewer at the Office of In Vitro Diagnostics Device Evaluation and Safety at FDA's Center for Devices and Radiological Health, recently noted that the FDA might take longer than usual to review pre-IDE applications, because "companion diagnostics have just exploded" (PGx Reporter 09/22/10).
However, while many firms might be in the early stages of discussing potential Rx/Dx strategies with the FDA, the Tufts report revealed a more sober picture of the current use of diagnostics in late-stage drug development.
According to the report, less than 10 percent of companies surveyed have compounds in late clinical development — between Phase IIb and Phase IV — that are being investigated with companion tests.
"While most companies believe companion diagnostics are needed for therapies to be truly personalized," drug firms don't seem to like the idea of including diagnostics on a drug's label, particularly when the treatment does work for a large portion of the general population, the report noted.
According to Milne, the companies he interviewed "generally would prefer that diagnostics be used for patient selection more so than patient monitoring, which can add barriers in terms of time, convenience, and cost to treatment."
It is well established that drug firms and diagnostic companies have divergent business models and product development timelines that often pose significant challenges to developing combination products.
"Companion diagnostics can present a problem for marketing products in less developed countries because central lab services tend not to be readily accessible, and not enough personalized medicines are in global markets to determine willingness to pay by pricing and reimbursement authorities," the Tufts report points out.
Pharma companies have tried to overcome the distribution barrier by working with diagnostics developers with access to extensive laboratory networks and marketing channels. Global drug giants have stated that diagnostic partners must have capabilities to accommodate the drug developers' multinational operations (PGx Reporter 04/14/10).
Among drugmakers pursuing personalized approaches, oncology is the strongest area of investment, according to the Tufts study. In oncology, "R&D relies on more biomarkers and diagnostics [and] company infrastructures have been changed to incorporate this approach into oncology programs," the report states.
"One interviewee said he expects all oncology drugs will have a related diagnostic 'within five to 10 years,'" the report adds.
The survey also identified cardiovascular, central nervous system, and immunologic treatments as areas where personalized medicine is "making headway" at drug firms. Meanwhile, personalized medicine is still "just getting started" for metabolic and respiratory therapies, as well as in virology, the Tufts researchers found.
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