The barriers to personalized medicine

Pharmaceutical Technology Europe interviews Richard L. Hudson, CEO and Editor of Science|Business, a London (UK) and Brussels (Belgium) based innovation network that has been researching the promise and problems of personalised healthcare in Europe, with partners at Sweden’s Karolinska Institutet and a range of healthcare companies and organisations.

How has personalised medicine evolved during the past 5 years?
This is a challenging technology — disruptive to the whole delivery chain of one of society’s fundamental services, healthcare. With it, we move from a ‘one-size-fits-all’ system to a targeted approach for sub-groups of patients; so a change like that is, inevitably, going to be slow, but it is coming, and Science|Business and its partners have been conducting extensive research over the past year on the scope and pace. As the European Medicines Agency (EMA) put it in a report earlier this year: “The concept of personalised medicine is rapidly moving from a theoretical concept to an everyday reality.”

Perhaps the most immediate changes have been in the conduct of clinical trials for new drugs and in fundamental disease research. Increasingly, new diagnostics are being developed to quality patients for participation in trials. One example: Pfizer and Qiagen are co-developing an assay for patient enrolment in a glioblastoma trial. Gary Firestein, dean of translational medicine at the University of California, told us that biomarker-based trials can involve fewer than 20 patients, are much faster and cost less — approximately $500,000 apiece. It doesn’t remove the need for big, expensive trials; but it does promise greater efficiency and is attracting the attention of industrialists and researchers alike.

There is also a growing number of products approaching the clinic, or already in it in some countries. Of course, there are the well-established examples such as Herceptin diagnostics for breast cancer patients and sensitivity tests for warfarin anti-coagulant, but there are also new developments including:

• Pfizer and GSK have launched an AIDS drug, maraviroc, with an accompanying diagnostic by Monogram Sciences to test whether the patient’s specific HIV strain would respond to the medicine.
• Cancer Research UK and the Technical University of Denmark have announced a way to identify genes that prevent a common breast cancer drug, paclitaxel, from working.
• Novartis and Merck have been assessing the use of a protein marker, Kidney Injury Membrane Protein 1, to test the propensity of drugs to damage kidneys and as a test for early signs of acute kidney injury.

The list is lengthening. In the US, the Personalized Medicine Coalition estimates that in the past 3 years the number of products has risen to 37 from 13.

How much attention are Big Pharma companies paying to personalised medicine?
A great deal. It’s both exciting and scary for industry — much like the way personal computers and the Internet turned the electronics, computing and media industries upside-down, creating new winners and losers.

You see lots of business experiments under way now: joint ventures, cross-licensing, new business units, etc. Most intriguing is the way ICT and electronics companies are moving towards the pharma world, and the pharma companies towards them, as they try to understand the new technologies and business models. GE Healthcare, Microsoft — this kind of company is suddenly very popular in the pharma world because of their skill at devices, diagnostics, information processing and other fields that traditionally have more to do with silicon than carbon. I wouldn’t be surprised if, 5–10 years down the road, we move beyond tentative cross-industry ventures and into full mergers. It happens in every other industry, when disruptive technologies upset the old order.

What are the main barriers holding back progress?
There are many. To understand them, we and researchers at Stockholm’s Karolinska Institutet — led by Associate Prof. Carl Johan Sundberg and research assistant Danielle Lewensohn — conducted an opinion survey of health professionals this past winter in four countries: the UK, France, Belgium and the Netherlands. The barriers, according to respondents are:

• Of the health professionals (researchers, industry execs, doctors, hospital administrators, regulators and payers) surveyed, 80% saw the identification of biomarkers as a significant barrier to progress. About 71% called ‘basic understanding of biology’ another significant barrier. So the science isn’t by any means finished yet.

• Beyond science, the biggest barrier is finance. 78% identified insufficient investment and funding as a significant barrier (interestingly, patients advocates and researchers included in the survey felt most strongly about this).

• 63% say the absence of clear regulatory guidelines is causing delay. Not surprisingly, industry executives feel this most strongly, but patients advocates fully agree with them. Only the regulators and doctors express less concern about this barrier.

Personalised medicine will require a change in business models. What will companies have to do to stand any chance of being successful?
In truth, nobody knows: medicine is an unusual service in that it is so controlled by regulation and the public sector. The technical issues will be resolved; that’s a challenge well within the capability of the pharmaceutical industry, biomedical researchers and the wider business world to solve, but the wild card is the public sector.

Economic logic would suggest the winners will be those who can acquire or form multi-disciplinary partnerships, to develop the diagnostics and the treatment in tandem — plus the information systems to manage them. However, health agencies and insurers don’t presently buy or authorize treatments in the same, multi-disciplinary fashion. Devices and diagnostics go down different regulatory and reimbursement paths than do drugs; they draw on different budgets. Even today, for breast cancer treatment, in many European countries Herceptin diagnostics are simply not used by doctors, or not reimbursed by the insurers or health services — despite years of evidence that tandem diagnostic/drug treatment is vital to the treatment’s success.

This puts the industry in the awkward position of seeing a business case, but not yet knowing whether the returns will be high enough to justify sweeping change. Hence, the current proliferation of case-by-case ventures and partnerships: Don’t get left behind, but equally don’t yet bet the whole company on it, is the conventional wisdom so far. This leaves orphan drug companies, like Genzyme and Amgen, well placed.

What kind of changes will need to occur in health systems before personalised medicine can further evolve?
Reform the way medicines and diagnostics are purchased and administered. Educate doctors and hospital administrators about it. Most of all, step up engagement with these new technologies.

A case in point is the perceptions about the costs and benefits of personalised healthcare. Our survey found overwhelming support for the view that it will benefit patients — more than 80% of the healthcare professionals we surveyed predicted it will reduce medical errors. It will avoid adverse effects of treatment and generally approve patient outcomes, they said. However, cost is an issue; in the short term (5 years), 58% expect new technologies to increase healthcare costs, but in the long term (15 years), a plurality (46%) said they expect it to lower costs. So there is a perceived ‘hump’ to get over in the next few years.

Are any activities/initiatives taking place across Europe or others parts of the world to help overcome the barriers facing personalised medicine?
A great deal, but to focus on the European level, a recent buzz of activity at the EMA is emblematic. Last year it published guidelines for development of biomarkers and this year it is developing its first guidelines for the use of this technology in pharmacokinetics — how drugs are absorbed, how quickly they work and how soon eliminated. These factors differ by patient group, and new labelling and prescription information could help doctors improve treatment.

That there should be a European dimension is a widely held view. Our survey found 80% support EU coordination, which is a pretty radical view given that by EU treaty, the provision of healthcare is a national, not European Commission, responsibility. This technology could end up being disruptive for European politicians, as well as healthcare providers.