John C. Lechleiter, Ph.D.
President and Chief Operating Officer — Eli Lilly and CompanyNovember 29, 2007
Conference on Personalized Medicine: A Call to Action — Boston, Massachusetts
Markets of One: The Pharmaceutical Industry and The Pursuit of Personalized Medicine - (Slides)
The rise of personalized medicine is one of the most important developments in health care today … and you’ve brought together the right mix of sponsors and experts from academic medicine, business, and patient care settings.
Of course I’m pleased that you saw fit to include someone from a major pharmaceutical company as well. Personalized medicine will change health care almost across the board … but nowhere, I would argue, are the cross-currents of change more powerful – or the stakes higher – than in the development, manufacture, and sale of prescription medicines. In my industry, we would be powerless to resist personalized medicine – not to say foolish.
For that reason, we at Lilly remain mystified by the skepticism that persists around the questions: “Are the drug companies really on board with personalized medicine? And will their business models accommodate products more finely targeted to patient groups within a disease category?”
I can only speak for Eli Lilly and Company but my answers to those questions are, “Yes, we’re not only on board but also trying to serve as a kind of conductor, helping to coax others on board. And, yes, our business model will accommodate personalized medicine. It may in fact depend on it.”
I’d like to use my time here today to elaborate on those contentions.
Let me start by challenging the widespread notion that personalized medicine is entirely, or even primarily, about unlocking the secrets of the human genome. Genomic medicine certainly serves to extend and hopefully to accelerate our goals but the promise of personalized medicine is actually much broader and much more deeply rooted.
Contrary to popular perceptions, the pharmaceutical industry has rarely pursued “one-size-fits-all” strategies in our promotional efforts. Segmentation of disease categories and patient groups has long been the norm. Today, however, what’s fundamentally different is the availability of tools, technologies, and new knowledge to inform such segmentation and to render it more relevant and meaningful.
The concept of the “biomarker” is a good example. Biomarkers – as telltale indicators of biological activity that help to guide treatment decisions – are nothing new. Longstanding measures such as HbA1c levels to determine appropriate diabetes regimens … or cholesterol levels to assess the possible benefit of statins – each of these are biomarkers.
Today, biomarkers are more pervasive and sophisticated than ever before, and they are coming into play at much earlier stages of drug development.
At Lilly, fully 90 percent of molecules reaching the clinical development stage now have a biomarker strategy associated with them – representing a dramatic increase over the last several years.
That’s already generating some important benefits for the company’s R&D processes – allowing us, in some cases, to weed out unpromising molecules earlier in game; to compress development timelines; to run smaller, more focused clinical trials and to adapt them mid-stream, based on what we’re seeing, and to start exploring secondary indications more quickly.
As a result, over time, we hope that one of the beneficial effects of widespread biomarker application will be shorter cycle times and lower costs in drug development.
The growing use of biomarkers, it must be said, is but one aspect of personalized medicine. To capture the broader significance of where we see health care going, we’ve coined our own term at Lilly … and that’s “tailored therapeutics.”
The notion of “tailoring,” we believe, goes beyond typical understandings of personalized medicine in two important ways: First, there are many different types of personalized health care. And, second, there can be wide variation in the degree of personalization.
The tailoring analogy helps to make this clear.
A traditional tailor can sew up some cuffs, extend the sleeves, or even – on very rare occasions – take in the waist. In that same spirit, tailored therapeutics can narrow the target population of patients, tighten up dosing guidance based on various criteria, address the timing of therapy, or provide better information to patients – for example to improve adherence. And, of course, none of these scenarios is mutually exclusive.
With regard to the degree of tailoring: There’s quite a range between buying whatever’s on the rack and ordering a custom-made suit – just as there’s quite a range between “one-size-fits-all” medicine and truly patient-specific therapies and treatment regimens.
While yesterday’s punch line was, “Take two aspirin and call me in the morning,” in another few decades we may all be taking medicines tailored to our own personal genome. Meanwhile, in between these poles – that’s where the action is!
Those insights are very important for us as a pharmaceutical company – and I believe it applies more broadly – because we don’t want anyone inside Lilly to believe that tailored therapies are someone else’s problem. When you understand the diversity and the wide spectrum of personalized medicine, then you realize that it has implications in the labs and clinics, certainly … but also in manufacturing, sales and marketing, and all kinds of external relationships.
I’d like to give you some examples of tailoring from Lilly: an early-stage effort, and two examples that involve existing products.
In 2004, Lilly acquired a San Diego-based company known as Applied Molecular Evolutions (AME) in order to tap its technologies for customizing antibodies and proteins. With the help of AME, we have quite literally designed a molecule that may help treat the large percentage of patients who do not respond as well to Rituxan – which is used to treat non-Hodgkin’s lymphoma. Of course, the molecule still needs to prove itself in the course of clinical development.
Efforts to tailor do not end with product approval. We’ve learned a great deal in actual practice about a Lilly drug for severe sepsis, Xigris, since we launched it six years ago. Xigris has proven to be a life-saving drug, but doctors have had trouble identifying the patients who are most likely to respond favorably to it. So, we’ve formed a diagnostic partnership with a company called Biosite, which is developing a diagnostic test that can be used at the bedside – to help doctors better identify the right patients for Xigris and the right doses throughout the course of several days of treatment.
Finally, Strattera, Lilly’s product for Attention-Deficit/Hyperactivity Disorder, is another interesting example. It’s the only non-stimulant drug approved to treat ADHD. In the general patient population, Strattera has a response rate somewhat lower than the response rate to the stimulants. However, analysis of clinical trial results and other data has shown that for ADHD patients with co-morbid anxiety, the response to stimulants drops – while the response rate to Strattera stays about the same.
So: we’re working to help doctors identify the one-third of ADHD patients who also suffer from anxiety and to highlight Strattera’s more favorable profile for this population compared to other products.
Let’s go back over the examples now – to tease out a few of their business implications:
- In the case of the AME compound, if it’s successful, the drug probably would be of interest to doctors treating patients who don’t respond well, today, to Rituxan – a reasonably well-defined market.
- In the case of Xigris, the ability to identify patients most likely to respond … in turn helps assure payers that the large cost of this biotech therapy is matched with excellent clinical outcomes.
- And with regard to Strattera, tailoring turns what might be seen as a slight disadvantage in perceived efficacy among the general population into a clear advantage among the target group of patients.
Good medicine lines up with good business in every case – and the common denominator is increased value.
I’d like to elaborate a little bit further on this increased value proposition, which is really the heart of the business case for personalized medicine.
As you know – throughout the industrialized world – health-care costs have been growing at a rate that most observers believe is unsustainable. Even when health care is recognized as valuable, it’s increasingly hard to handle the bill. In many cases, however, the value of health-care products and services is actually in question – as this slide demonstrates.
Now, I could give you an entire speech on the unfairness of this assessment where prescription drugs are concerned – starting with the fact that drug prices are much more visible to patients, coupled with the fact that branded prescription drugs are the only source of generic medicines that I know of. But we have more to gain by seeking to understand this data and acknowledging the legitimate sources of disappointment.
Here’s a big one. Prescription therapies can work miracles in many patients, but in other patients they don’t work at all. And the practice of medicine, too often, is reduced to trial-and-error – in the effort to figure out which patients will respond to which therapy.
And for a number of reasons, the safety bar in the regulation of prescription medicines has been raised to an all-time high. As most of you understand, no medical treatment … none that really works … is 100 percent safe and without side effects – not even the aspirin I took this morning. However, even as we argue for a reasonable balance of benefit and risk, those of us in industry know that we are the ones who will be held accountable – for trying to know and to share as much as possible about the workings of our products.
That summary, I hope, helps you to understand better why we believe that pursuing tailored therapeutics is imperative for us at Lilly:
- When we’re better able to target our products on the patients who will really benefit from them, then our value proposition will surely grow.
- When tailored therapeutics are used to reduce the trial-and-error nature of health care, then fewer resources will be wasted and the cost of health care will be more sustainable.
- And, as we begin to take advantage of the flood of health-care information and new scientific knowledge, we’ll gain a better understanding of how benefit and risk line up for individual patients.
Despite all of these potential benefits, there are still those who fear that tailoring … personalized medicine writ large … is a threat to our industry’s innovation model. If there are no more “blockbuster drugs,” the question goes, then where will the resources come from to pay for next-generation R&D?
At Lilly, to be honest, we’re not overly concerned about that. In the spirit of frankness, I’ll share with you here an analysis of what tailoring might mean for peak sales of a drug. Instead of getting a relatively small share of a really large pie – the traditional blockbuster model – a tailored therapy could expect to claim a relatively large share of a more segmented pie. Repeat prescribing and patient compliance almost certainly would occur at a higher rate – further supporting the economic case.
The net results, in terms of sales, actually look quite favorable.
And, we believe that in addition to this, there will be a bottom-line impact as well. The streamlining of R&D processes that I described earlier – resulting from the application of biomarkers and other tailoring strategies – should help us to limit operational costs.
Now, don’t get me wrong. Making this leap is a scary proposition. It has enormous implications not only for R&D but also for almost every aspect of marketing and strategy. But the companies that get it right will be better off than they were before.
Let’s think about what it will take to “get it right” in the broader sense – the changes that will be needed for personalized medicine to realize its potential not only in the pharmaceutical industry but throughout health care. For the sake of simplicity, I will group these expectations under three broad principles: Confidence, Clarity, and Collaboration.
Inside Lilly and the pharmaceutical industry, we’ll build confidence to the extent that we learn to understand what’s really in the way of optimal outcomes for individual patients – whether it’s resistance to the device that’s used to deliver a medication; failure to stick with important dietary requirements; an undiagnosed co-morbidity; the inability to pay for a medication, or any one of many other impediments.
To do that, we’ll need to see the world of health care as patients see it, which is a bigger leap than you might imagine. The pharmaceutical industry is, of course, quite accustomed to interacting with doctors and trying to understand their needs, beliefs, and preferences – but in all honesty we don’t have that depth of experience where patients are concerned.
Our sales forces and our ability to communicate directly with patients could well become more important than ever – but we’ll use these channels in completely new ways – focused on improving patient outcomes. For example, could you foresee a situation in which part of the compensation for pharmaceutical company sales representatives is in proportion to how much the average HbA1c level of people with diabetes in their geographic territories improves over the course of a year?
Before you snicker, this is indeed how some medical practices in Minnesota – through Minnesota Community Measurement – are bring ranked and rewarded today.
Developing a new level of familiarity with patients and their needs will improve our industry’s own confidence in personalized medicine – while making us better, all-round contributors to the health-care system.
Of course, confidence is a two-way street – and public confidence in the requirements and benefits of personalized medicine has a long way to go.
It needs to start with education about the nature of genomics and assurances about the collection and use of genetic data. Earlier this year, Lilly became one of the first two large companies (the other is IBM) to adopt an official policy that our employees’ genetic information can never be used to discriminate against them in employment or benefits decisions.
But actions by individual firms won’t be enough. I hope I’m preaching to the choir here, but passage of appropriate federal legislation on the privacy of genetic data clearly is overdue.
Privacy legislation is the first step in public education. Up until now, debates have focused almost entirely on the assumed risks surrounding data collection – risks to privacy and insurability, for example – with little recognition of the enormous benefits that the genomic revolution and personalized medicine can bring.
My second rubric – in talking about the changes that will help make personalized medicine a reality – is Clarity. In particular, I mean clarity in the regulatory environment – an essential role of government.
It starts with the clinical-trial process. In industry, we need clarity about the kind of evidence that will be required to support the approval of tailored therapies. We also hope for an acceleration of the Critical Path Initiative and its goals of smaller, more focused, more flexible, and more affordable clinical trials.
To promote widespread access to health data, there’s a huge need not only for the aforementioned privacy standards but also for technical standards that would encourage the proliferation of Electronic Medical Records and the interconnection of health-data networks.
It’s also time for standards to be established for data-mining and retrospective or pooled data analyses, so that such information might one day be used to support label claims and safety reviews in place of expensive new trials.
Clarity on the regulation of companion diagnostics is also important, as are the standards for clinical validation of diagnostics.
Finally, a new spirit of Collaboration is needed to help realize the promise of personalized medicine – collaboration among academia, government, and industry, but also within the private sector.
Clinical validation of biomarkers, for example, could be a shared responsibility, with industry focused on developing and testing companion diagnostics for new drugs while public and university-based researchers play more of a role in finding biomarkers for disease prediction and for legacy drugs.
Collaboration also means breaking down inappropriate barriers to health-data collection and access. Public payers, private health plans, drug companies, physicians and hospitals, and patients themselves all have particular reasons to be guarded in their collection and sharing of information but in truth, all would be better off – once patient privacy is assured – if insights from clinical practice were available quickly and easily.
Within the pharmaceutical industry itself, increasing collaboration is driven by a desire to use knowledge more effectively. One laboratory’s discarded failure may be the missing puzzle piece in another lab’s effort to understand a particular patient group or a disease pathway.
Pharmaceutical companies need to remain as proud and as guarded as ever about our intellectual property – the basis of our survival – but I also think that we need to look for new ways to collaborate and to share information and insight, when the family jewels are not at stake and where anti-trust laws allow.
The growing transparency around our clinical trial results in pharma is a step in the right direction. In 2004, our company became the first to disclose the results of all our clinical trials – on the Internet. At the time, it was a somewhat frightening step to take but, as others have followed suit, it has not only helped us to learn from each other’s work but I think it also improved our credibility.
Sample banking is another good example of what can be done collaboratively to advance personalized medicine. At Lilly, we’ve been pioneers in building a state-of-the-art “bank” to house DNA, plasma, and tissue samples ? obtained with patients’ consent in the course of multiple clinical trials. This database, which currently holds more than 26,000 samples, will be a powerful resource in the ongoing effort to develop and apply new learning, using pharmacogenomics.
To tackle the huge challenge of Alzheimer’s Disease, we’re involved in large-scale collaborative work with other companies, academia, and government to improve brain imaging techniques, establish standards, and share imaging data.
Well, I hope I’ve persuaded you that at least in our corner of the pharmaceutical business, we’re serious about serving “markets of one” and seizing the promise of personalized medicine. I wish I could invite you inside the business right now to drive my arguments home.
In fact, we’re rolling out a new vision inside Lilly at this very moment, drawing heavily on the insights and recommendations of our employees around the world. In this new vision, Lilly’s success as a business is defined in terms of our impact on individual patient outcomes – emphasis on the individual.
That’s the ultimate promise of personalized medicine – it’s about the individual patient – and we’re preparing to stake our business on realizing that promise.
Improving individual outcomes, as I’ve said, means tailoring our therapies for the patient populations in which they clearly work – and in which their potential side effects are not out of balance with their benefits.
It also means having courage to measure our products against other treatments and – favorable or unfavorable – accepting clear results as an appropriate basis for how our new therapies are used and perhaps even priced.
It means learning to communicate with patients – sometimes directly and sometimes through doctors or payers – not primarily to pitch our products but rather to educate them on how lifestyle factors, genetic characteristics, co-morbidities, and adherence to larger treatment plans all contribute to health outcomes.
This adds up to a very tall order. But the promise of personalized medicine – or, to use the Lilly term, tailored therapeutics – makes this a very exciting time to be part of health care.
If we’re successful, then I’m convinced that both patients … and Eli Lilly and Company … will be better off.
