22nd European Association for Cancer Research, Barcelona, 8th July 2012

The changing field of drug development

Dr Jonathan Yingling – Oncology Drug Discovery, Eli Lilly

Can you tell me a bit about the talk you’re giving today?

Sure, I was talking about drug discovery and development and the changing paradigm that we find ourselves in as an industry and as a scientific community and really trying to cover just the general drug discovery process, if you will, from our ability to identify relevant targets in cancer biology, develop molecules against those, so either small molecule or large molecule therapeutics, and then, more importantly recently, the evolving paradigm of being able to select the right patient populations in order to evaluate those molecules to expedite and deliver innovative medicines to patients in a more efficient fashion.

So what are some of the key issues?

There are lots of issues and a lot of progress against those issues. One is really the changing paradigm of being able, rather than treat the general population and look for minor incremental benefits in those populations of patients, really being able to molecularly characterise patient populations a priori and then match the therapeutics that we have in our arsenal of pharmaceutical innovative medicines to those patients in a more targeted fashion.

You’re talking a bit in your talk about what needs to change and what changes can we see?

There are changes not only within the pharmaceutical industry in the way that we approach drug discovery but also the changes in the evolving regulatory landscape and the regulatory environment in which we find ourselves. There have been successes in the last year where companion diagnostic tests have been delivered along with a therapy, crizotinib and zelboraf being the poster children if you will, in recent times for those opportunities. The regulatory environment, we’re all learning how to do this in a more effective fashion, both from a drug discovery perspective within the pharmaceutical industry itself as well as our interactions with the regulatory authorities that ultimately are necessary in order for us to bring innovative medicines to patients.

So is it a cordial working relationship with the FDA?

It’s a partnership, it’s definitely a partnership, and that partnership really needs to extend into the basic science arena as well. So the opportunity for us to be able to leverage the molecular analysis of patients and patient disease, really starts with a fundamental understanding of basic biology and the targets linked to various disease pathogenesis and pathology, giving us an opportunity to then make medicines or make molecules that target those. So it’s a partnership along the entire value chain from the basic science into the pharmaceutical and biotech industry and then ultimately with regulators with payers and with physicians that sit in their office on a daily basis trying to understand how best to treat their patient and our ability to help them and give them the tests as well as the therapeutics that they can match an individual patient with an individualised therapy is the way of the future.

Are there examples already where this has happened with small molecules and MAbs?

Yes, the most recent examples are, as I said, the zelboraf and crizotinib, Gleevec being the very first example back with CML in 1994 when it was initially approved. I think what we’re learning as an industry and in partnership, again, with basic scientists as well as with the regulatory authorities is how to do this more predictably and more efficiently into the future. It’s a journey, we’re at the early stages of that journey but I do believe in oncology we’ve now turned the corner in being able to do this more routinely.

So how should biomarkers influence trials then?

We need to understand the variability associated with the biomarker. When it comes to making treatment decisions around a particular biomarker or including or excluding patient populations from therapy, the reliability of the biomarker and the validation of that biomarker for the decision that’s being made is something that we can’t take lightly. So the rigour with which we evaluate the safety of our molecules, the efficacy of our molecules, we need to develop it and ensure that the same level of rigour comes with the tests that are developed for the biomarkers, that they are reliable, that they give the right information to physicians in order to make those decisions. There’s a whole science that comes along with that biomarker test, the biomarker assay, the validation of those assays that we need to pay very close attention to.