As a stem cell biologist, I was very excited when Nobel laureate Dr. Shinya Yamanaka of Kyoto University developed cellular reprogramming, which enables us to generate patient-specific, induced pluripotent stem cells (iPSCs).
Being pluripotent, these cells have the potential to make any cell or tissue type in the body. Being patient specific, tissues derived from these cells could sidestep immune rejection.
iPSCs ushered in the new era of personalized medicine, opening the door to customizing regenerative medicine and drug development.
That is until Yamanaka, a physician, responsibly put the brakes on his own technology. He argued that health-care systems, including Japan’s, couldn’t afford the personalized medicine approach.
Yamanaka instead pushed the concept of precision medicine and leveraged Japan’s competitive edge of having a relatively insular population. He argued that a biobank of 75 human iPSC lines would have a good enough immunological match to be tolerated by 80 per cent of the population. Based on this concept, Yamanaka is building a team of transplant scientists who are using iPSCs in clinical trials to treat a variety of age-related degenerative diseases.
Patient iPSCs can also be used to understand disease etiology (set of causes) and to develop drugs. In Japan, Yamanaka has amplified this concept significantly by creating a biobank of disease iPSCs and collaborating with the Japanese pharmaceutical company Takeda to use disease iPSCs as a platform for developing new drugs to treat diseases.
iPSCs can be used to improve the accuracy of existing drugs, which often have adverse reactions. Drugs have a sweet spot for optimal activity, yet as individuals we respond differently partly due to our varying ability to metabolize xenobiotics. Using patient iPSCs, it’s now possible to divide patients into responder classes. This new precision medicine approach will help to better stratify drug treatment groups.
While western jurisdictions also have begun to use iPSCs, the jury is still out on whether we’ll take a personalized or precision medicine approach. Because western countries have more diverse populations, we don’t have the competitive advantage that Japan has.
In Canada, we’re talking a lot about precision medicine, and that’s because we know that we can’t afford personalized medicine. However, there are early indications that we’re also putting the brakes on precision medicine.
One place where precision medicine has been practised for over a decade is in cancer treatment. For example, researchers are beginning to parse the different kinds of breast cancer based on molecular marker profiles. Each kind predicts a general trajectory of disease, a treatment strategy and a patient’s prognosis.
Of course, patient stratification is a work in progress, as researchers continue to subdivide the subdivisions to improve the precision of treatment plans. Oncology aims for a future where generalized approaches such as radiation and chemotherapy are replaced with more targeted therapies based on stratification. A stellar example is the biologic Herceptin, which shuts down a specific sub-class of breast cancer.
The only problem is that Herceptin and other biologics, which are being used to treat stratified sub-disease classes, are expensive. Unlike classic drugs, which are mass produced using chemistry, biologics are mostly human protein produced in bacteria (expensive) or mammalian cells (really expensive) using recombinant DNA technology and bioreactors.
Biologics are the tip of the iceberg because stem cells will be the next thing coming down the pike.
While the quality control of scalable chemistry is relatively straightforward, regulators apply more scrutiny to the scalable production of biologics, which adds significantly to costs. This is also why the off-patent generics in this class, biosimilars, are also going to be expensive.
The good news is that most biologics can deliver a knockout punch to a disease, if administered to a properly stratified disease class. This is their value proposition. However, a course of treatment can cost upwards of $50,000 a year, which is also beginning to look unsustainable.
To fight costs, Canadian patients are being denied coverage for biologics until all other (less expensive and less effective) measures are explored. The latest stunt I’ve heard of is that health-care systems are deliberately avoiding diagnostic tests that would stratify patients into “biologics-worthy” classes. This way, patients are kept in the dark about optimal treatment plans unless, of course, they can afford go to the Mayo Clinic for a second opinion.
More important than negotiating the cost of drugs via a national drug plan, Canada needs to develop a biologics strategy. For example, Canadian companies can be mobilized to create biosimilars reproducibly and at a high enough quality to ease Canadian regulatory scrutiny and drive down the cost of these important precision medicines. If not that, then perhaps Canadians need biologics insurance.
In the meantime, if Canada is going to stonewall biologics, then why are we even talking about precision medicine?
Derrick Rancourt is a professor in the University of Calgary’s Cumming School of Medicine, where he chairs the Graduate Science Education’s Professional Development Taskforce.