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Medicine gets personal: Sidney Taurel discusses tailored therapeutics

The future of the pharmaceutical industry lies in its willingness to share scientific information, tailor drugs for individual patient groups and have the courage to walk away from some therapies in order to improve outcomes in other areas, says Eli Lilly and Company chairman of the board Sidney Taurel. Addressing the Economic Club of Phoenix recently, Taurel expressed excitement at the possibilities ahead for new ways of developing medicines that cut costs and more precisely target which patients will benefit.

2008-12-03

The future of the pharmaceutical industry lies in its willingness to share scientific information, tailor drugs for individual patient groups and have the courage to walk away from some therapies in order to improve outcomes in other areas, says Eli Lilly and Company chairman of the board Sidney Taurel. Addressing the Economic Club of Phoenix recently, Taurel expressed excitement at the possibilities ahead for new ways of developing medicines that cut costs and more precisely target which patients will benefit.

Personalized medicine, which Taurel called nothing short of revolutionary, uses such tools as biomarkers (biochemical features that indicate the presence and progress of disease or the effects of treatment) to determine which patients will respond best to which medicines. The right drugs can then be delivered to those patients, rather than taking a one-size-fits-all approach. Profits would not be sacrificed, Taurel assured his audience of business people.

The luncheon was hosted by the W. P. Carey School of Business. "Instead of getting a relatively small share of a large pie," he said, "tailored therapy could expect to claim a relatively large share of a smaller pie. Repeat prescribing and patient compliance almost certainly would occur at a higher rate, further supporting the economic case. The net result in terms of sales turns out to be quite favorable."

Right drugs for the right patients

Speaking at times like a businessman and at times like a scientist, Taurel said Lilly's goal will be to ensure that all patients who should use a drug really do use it and, just as critically, that patients who should not use a drug do not use it. Accomplishing that objective, he said, "will depend quite literally on walking away from some business. This does not mean that our sales forces or direct-to-patient advertising will go away. In fact they could become more important than ever."

Drug representatives, for example, might receive incentives for patients' progress using the drugs they recommend. The old industry model of prescribing drugs for a large patient population with mixed results is due for a change, said Taurel, who served as CEO of Lilly from 1998 until March of this year. Patients are too often disappointed with their treatment, he said, and with good reason.

Efficacy rates of medicines prescribed for some of the most common illnesses average around 50 percent. That means some are more effective than 50 percent, but some are far less. Drugs for reducing cholesterol, for instance, work about 80 percent of the time, Taurel said, while many cancer drugs are only 20 percent effective. "There will always be some trial and error in the practice of medicine, but certainly we can do better than 50/50."

Health care costs a factor

Getting it right has become crucial as health care costs soar. Taurel spoke of factors both pushing and pulling society to do more to curb those costs while sacrificing nothing in the quality of medicine. The factors that push the traditional order in a new direction are being accelerated by technology pulling the industry toward change.

Health care costs are rising at a rate "most people think is unsustainable," Taurel said. "Human aging," he said, is the cause: three elements have converged in the last half-century. First, the industrialized world's post-World War II baby boom exploded the population. Second, the baby boom was followed by radically lower birthrates since the 1970s.

Third, improved public health infrastructures, better treatment options for diseases, and pharmaceutical innovation have led to an increase in life expectancy around the world. "The result of all these developments has been nothing less than the inversion of the age pyramid, standing it on its head," Taurel said. "It is most pronounced in Europe, where today already there are more people over 40 than under 40."

World's population is aging

This inverted age pyramid exists across the developed world and is becoming more pronounced. By 2030, the median age in Europe will be nearly 50, said Taurel, who was born a Spanish citizen in Morocco. In other words, too few young people are supporting too many old people. The traditional health care payment model, he said, is to have large numbers of young workers sustain a small number of retirees.

The result? "Medicare is facing an unfunded liability of around $30 trillion dollars in the decades ahead," Taurel said. Not only institutions are facing a squeeze. Individuals, too, are feeling the pinch when it comes to paying medical bills. Unfortunately for companies like Lilly, consumers don't always realize how the system works. Taurel cited a survey that found 62 percent of consumers rate generic medicines as good value, compared with just 22 percent who believe branded prescription drugs are a good value.

He called such assessments "unfair," pointing out that branded drugs subsidize generics. "I could also point out that prescription medicines only account for 10 cents on the dollar of health care spending in the U.S., and pharmaceutical treatments reduce costs elsewhere in the system, shortening or eliminating the need for institutional care, which is much more expensive," he said.

Reduce waste, improve value

The goal, he said, should be to reduce wasted spending while improving what he terms "the value proposition" of Lilly products. And that requires personalized, or tailored, medicine, as well as educating the public about compliance and expectations. As an example, Taurel used a typical diabetic patient.

Too often, the effectiveness of treatment is measured only in laboratory terms such as glucose levels and other disease markers detected through blood work. But if a medicine is working, the patient is unlikely to express satisfaction that his Hemoglobin A1C (a measure of blood glucose levels) has decreased. Instead, he'll report non-clinical indicators such as increased energy, more physical activity, playing tennis with the grandchildren.

"Other things start to matter more, such as injection devices which are easy to use or dosing regimens that make patients more likely to comply with doctors' orders," Taurel said. Those aspects of treatment, he said, must be improved so that the full value of drug products can be realized. If patients don't properly use their drugs, effectiveness declines.

Technology exerts its pull

At the same time that high prices are pushing us into personalized medicine, several factors are pulling us. Taurel noted that the Human Genome Project is probably the highest profile milestone recently in the life sciences. It allowed scientists to pin down and locate the chemical composition of every human gene. The effort did not reveal the hoped-for genetic "master code" that would unlock all the secrets of the human makeup.

Instead it showed that biological systems causing disease are even more complex than imagined. Still, Taurel suggested, as more pieces of the puzzle are revealed, it is within our grasp to target subsets of patients unaffected by earlier treatments, to understand why some therapies are not universally effective and share that knowledge with doctors. "The result would be fewer treatments that are costly and futile and fewer patients with dashed hopes," he said.

Drugs tailored to suit patients

Using the tailoring analogy, Taurel highlighted some Eli Lilly drugs that illustrate his enthusiasm for the new frontiers of science. Like a tailor altering a suit, lengthening sleeves, shortening cuffs, taking in the waist, so scientists can customize antibodies and proteins to come up with new molecules to treat disease, he said.

Studying the relationship between those new molecules and sets of biomarkers can help researchers determine more quickly and with greater precision whether the molecule deserves further testing and for what kind of diseases and patient population. Tailoring shapes not only treatment but also clinical trials, he said. Along with Japanese partner Daiichi Sankyo, Lilly has been developing Prasugrel, a drug to treat acute coronary syndrome.

The product is currently under review by the FDA. Late-stage trials for Prasugrel revealed much about the kind of patients most likely to benefit from the medicine as well as a precise knowledge about how to adjust the dosage to optimize the result in specific groups of patients. Another Lilly drug, Xigris, is used to treat severe sepsis, or a systemic reaction to infection that is fatal in about a third of patients who contract it.

Taurel said Xigris is effective in 20 to 40 percent of recipients. Because it is expensive and has side effects, doctors want to more precisely pinpoint which patients are most likely to benefit. So Lilly has formed a partnership with a company called Biosite, Inc., which is developing a diagnostic test to better identify the right patients for Xigris and the right dosage. Tailoring is now used widely in Lilly drug research.

"More and more, our goal is to give doctors the ability to prescribe for individual patients with a much higher level of confidence the right dose of the right medicine at the right time," Taurel said. "This is really what we are all about. By doing this, we will increase the therapeutic value of our products and greatly reduce the economic toll exacted by spending on medicines that don't work."

Ensuring success

What will it take for this so-called revolution to succeed? Scientists first must learn what stands in the way of positive outcomes for patients, whether it's the device used to deliver the medication, failure to comply with dietary restrictions, or the inability to pay medical bills. The public must have confidence in the requirements and benefits of tailored drug therapies. That begins with education about the nature of genomics and assurances about the collection and use of genetic data, Taurel said.

Last year, he said, Lilly became one of the first two large companies (in addition to IBM) to adopt a policy that says employees' genetic information can never be used to discriminate against them in employment or benefit decisions. But will the public as a whole embrace exchanging their genetic fingerprints for improved drug treatments?

Altruism may play a role, Taurel suggested. "Up until now the debates on genetic information have focused almost entirely on the assumed risks surrounding data collection, risks to privacy and insurability, for example," he said, "with little recognition of the enormous benefits for the genomic revolution that tailored therapies can bring."

Finally, Taurel said, collaboration is vital for achieving the promise of tailored therapies — collaboration between academia, government, industry and the private sector. Even competing pharmaceutical companies should share knowledge for the benefit of all. "The promise of personalized medicine and tailored therapeutics makes this an exciting time to be part of the health care business," Taurel concluded. "If we are successful, it means both our patients and also our business will be better off."

Bottom Line:

Tailoring new drugs is used in three ways:

1. At the drug development stage, tailoring targets medicines to work on specific disease biomarkers in subsets of patients who will respond most favorably. This allows scientists to determine more quickly and with better precision whether the drug deserves further testing and for what kinds of diseases.
2. Tailoring shapes clinical trial work, further determining which patients benefit from the drug and what dose is optimal. Tailoring strategies help to reduce failure rates of drugs at late stages of development. Failures are the primary source of the high cost of research and development.
3. Once a drug has been approved and is in use, efforts to tailor the medicine to the individual continue in collaboration with doctors.

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