March 3, 2017

UK Pharmacogenetics and Stratified Medicine Network 2010

Hinxton 21st October 2010

An admission; the world of personali[s|z]ed medicine has always baffled me. I understand the science, and I'm as excited by its potential as the next person. My recent pharmacogenetics (PGx) involvement, however, has left me feeling that there is certain 'inertia' preventing the field living up to its hype. That's why this 1-day meeting was so timely; I am now enlightened, and ather more excited about prospects for what I will now term "stratified medicine". Unlike at the meeting itself, I'll start with the science, which came after lunch (this report is mosty reverse cronologically). Talks on PGx related to drug induced liver injury (DILI) by Ann Daly (Newcastle U) and Warfarin dose by Panos Deloukas (WTSI) and Andrea Jorgensen (Liverpool U) demonstrate genetic determinants of adverse drug responses (ADRs) and drug metabolism. And the talk on stratification of cancer medicines by Peter Johnson (CRUK) demonstrated the clinical utility of companion diagnostics (KRAS/cituximab and EGFR/Gefitinib). So there we have it - no panacea, but stratified medicine has an undeniably solid foundation, and some established poster children. Today's witness for pharma is Chris Chamberlain (AZ), and he ticks all the right boxes; the upside of StratMed being better utility/quality of drugs, and the downsides being increased time/cost of development. Although the overall effect on revenue is uncertain, AZ predict much higher return for co-launch than if the stratifier is introduced after the drug reaches market. Accepting that the genie is finally out of the bottle lends credance to his assertion that StratMed will now percolate throughout AZ's entire development portfolio. In addition to the business case, he gave thoughtful consideration to the operational complexities of PGx; their informatics are currently ill-equiped for managing the next wave of high-dimensional high-throughput genomics data... which leads nicely to (from?) the previous talk of the day... ...The Technology Strategy Board (UK funding agency, represented by Joe McNamara and Angela Flannery) have cash to spend on Stratified Medicine, including some earmarked specifically for development of a  tumour profiling data management platform. The idea is to leverage the UK's single healthcare system by creating a resource that mediates data from hospitals and testing labs on one side, to academics/industry research users on the other, thus enabling the UK StratMed industry and creating wealth all round. So we have covered the academics, pharmas and funding agencies, and touched on biotech and NHS (and the regulator has a final cameo). All we need is someone to bring it all together. Of the various PGx research networks worldwide, NIH's is by far the best established/supported, as presented by David Flockhart (U Indiana). One key message here, in common with many of the other talks, was the importance of informatics, exemplified by the NIH-funded PharmaGKB (meta data curation proves more valuable than experimental data consolidation yet again, but that's a story for another time). Although a branch was held out to pharma early on, the NIH network is now entirely academic in makeup; perhaps the time was not right back then, when the potential of PGx to "split the blockbuster market" seemed a significant risk. However, on a fine Autumn day in Hinxton in 2010 there seemed like a great deal of synergy between all of the StratMed stakeholders, a sentiment that will hopefuly be captured by the UK PGx StratMed network, with Munir Pirmohamed (Liverpool U) giving the meeting's opening talk. The idea is for the multi-disciplinary constituency (pharma, diagnostic, IT, academic) to consolidate around a vehicle that;

  • Helps identify partners for collaboration
  • Disseminates best practice
  • Provides advice on regulation, education, and to press/media,
  • Lobbies for funding,
  • And participates in many other worthy activities.

And, thanks to the unique perspective of the meeting, my personal fog lifts. I now believe that StratMed is destined to revolutionise medicine for the better, and agree that this is what all participants are striving to achieve. So where is the bottleneck? It's subtle; genes are far more democratised than small-molecules or antibodies - you can't protect a genetic association (biomarker) by patent. Lack of protection reduces the financial incentive needed to offset the significant investment in informatics. This explains Stephen Little's (Quiagen) assertion that MDx companies are not interested in "discovering" biomarkers and Chris Chamberlain free admission that AZ have no interest in developing diagnostic tests. In this 'cost neutral' environment, the real beneficiaries, other than the patients, will be the healthcare systems (e.g. the NHS) themselves. I think that the current TSB and CRUK drives bear witness to the fact that the people driving policy have noticed exactly this! So, who better to bring together industry, academia and the NHS in search of stratified medicine than the UK PGx StratMed network? In view of my personal preference for all forms of open platforms, I will be delighted if this is the case. And finally the regulator; I did not get the feeling from Krishna Prasad from the MHRA that they're about to weild a big PGx stick any time soon, so it's down to the industry to sort this one out for themselves one way or another, for the time being at least.

Topics: Bioinformatics