In the first of a two-part piece, Turna Ray reflects on the Personalized Medicine World Conference, 2014 and the discussions held there around the state of drug development, recent advances in the field, scientific challenges facing the industry and the evolving regulatory and financial environment.
This is the first of a two-part feature on the state of personalized drug development. The first part focuses on the scientific challenges facing the industry. The second part will discuss the evolving regulatory and financial environment and recent advances in the field.
The head of pharmacogenomics at Takeda Pharmaceuticals, part of the largest drug maker in Asia, recently stood before a crowd of life sciences leaders in Northern California and told them that pharmaceutical companies have been doing it all wrong when it comes to advancing personalizing therapies. If the aim is to deliver ‘the right drug for the right patient,’ as the mantra goes, then development shouldn’t start with the drug, Eric Lai said at the Personalized Medicine World Conference in January 2014. It should begin with the patient.
Instead of mechanically following the well-worn three-phase drug development paradigm, where biomarkers, pharmacogenomics, and companion diagnostics enter the picture too late in the game, usually when the treatment doesn’t appear to work so well in a broader patient population, Lai advised industry colleagues to first identify the molecularly defined patient groups in need of effective treatments and work backwards.
He recommended his colleagues make more use of the big databases in which various groups are collecting an array of information on large cohorts. “You want to identify subgroups of patients from these large databases and from there, you’re going to take those subtypes and see if [they] correlate with phenotype in your clinical trial,” Lai said. “You have to start from the beginning and identify patients, not just the target.”
To illustrate his point, he cited the fact that 35 per cent of rheumatoid arthritis patients don’t respond to anti-TNF therapies or methotrexate. “What are the characteristics [of these patients], what are the targets for those patients? From there you think about what are your commercial needs. And now you identify the target,” he said.
At a life sciences meeting minutes from Google headquarters, Lai was preaching to the choir. After all, it’s not a personalized medicine conference until someone laments that the traditional ‘one-size fits all’ drug-making process is broken and then announces that low-cost genome sequencing will save the day. In a twist, Lai said, “Even if we have the technology to do personalized medicine…we don’t have enough drugs to give you personalized medicine. I don’t care how good your technology is.”
Although pharmacogenomic strategies are making a tremendous impact in oncology, in Lai’s view, the field of precision medicine won’t really take off until it can address the maladies that affect more, if not most, of us. “In order to do this you have to improve the drug development process…and you have to think about it very differently.”
In his stark assessment of the challenges for pharmaceutical companies developing personalized medicines, Lai is not alone. There are others in the drug industry who are also speaking out about much needed changes that must happen before individualized care is the care everyone receives, not just those with cancer or rare monogenic diseases. Kenneth Emancipator, director of companion diagnostics at Merck, has been making the rounds at various medical conferences—and making quite an impression—with his talk, entitled “It’s not just about the drug!”
It’s a talk in which Emancipator is relentless with the message that drug makers need to think from the get go not just about their compound—which is what they’re used to—but also about the test that will determine which patients will get their drug. Pharma companies now need to think about the technology of the companion test, how to validate the test, how to get it through regulatory approval, how to market the test, how to educate doctors about the drug and the test, and how to gain reimbursement…not just for the drug, but also for the test. Because if no one pays for the test, then there is no test, and no one gets the drug.
Then, there are complementary diagnostics to consider. These tests aren’t directly tied to making treatment decisions with a particular drug, but they can improve patient diagnosis, gauge which have worsening disease, and which can forgo aggressive, costly interventions. In this way, complementary tests can certainly impact the dynamics of a disease market a pharmaceutical company is selling its drug in.
When a therapy is in preclinical development, there may seem to be no reason to start thinking about a companion diagnostic. In Emancipator’s view, however, drug developers can’t start early enough when it comes to thinking about a companion testing strategy for an agent. The fact that top drug makers have all hired diagnostic executives like Emancipator to guide their personalized medicine strategies certainly signals some change in industry thinking. Still, pharma companies aren’t used to developing and marketing their drugs in the context of a diagnostic and they often aren’t prepared to face the complexity that a test adds into the process, said Peter Keeling, CEO of consulting firm Diaceutics.
“There’s still risk management going on within pharma. They’re still trying to develop drugs in all-comers first but studying biomarkers within that,” Keeling told PGx Reporter. Diaceutics specializes in helping drug makers plan out their personalized medicine programs and has overseen more than 50 such projects over the last eight years, involving drugs such as GlaxoSmithKline’s HIV treatment Ziagen (abacavir), Pfizer’s HIV drug Selzentry (maraviroc) and AstraZeneca’s non-small cell lung cancer agent Iressa (gefitinib).
“Despite the fact that you have some very successful targeted therapies on the market, which are billion-dollar brands, there is still the perception that you are subsetting your market by not going with an all-comers strategy” where the drug is studied in a molecularly-undifferentiated patient group, Keeling said. “That’s increasing the complexity and it’s increasing the risks.”
Of the projects Diaceutics has had input in, 60 per cent have been drugs that are being co-developed with a companion test, and 40 per cent are enabled by complementary tests for disease screening, monitoring and prognosis. The company estimates that 20 per cent of the Rx/Dx projects it has worked on have already come to market, approximately 50 per cent are still under development and 30 per cent of the projects have been discontinued because the biological hypothesis didn’t pan out.
The global pharmaceutical market is estimated to be worth $300 billion. Personalized medicine revenues currently total $20 billion, Takeda’s Lai estimated. “Personalized medicine is definitely growing in health care, but it’s still a small number,” he said at the conference.