Like an avid gardener longs for spring, I can’t wait for “personalized medicine” to blossom and burgeon. I’m a breast cancer patient — the term “survivor” is reserved for those who’ve been out of treatment and cancer-free for five years or more — and like millions of other women who’ve been diagnosed and treated “successfully,” there’s a part of me that’s always on guard, waiting for the other shoe to drop. Why? Because despite all the research that’s been done on breast cancer in recent years, many key questions about what ignites it and what determines its risk of recurrence remain unanswered.
Image courtesy of
Michael Ermarth, FDA
The same is true for hundreds of diseases, from cancer in its myriad forms to autoimmune diseases such as lupus and rheumatoid arthritis, to neurological disorders such as Parkinson’s and corticobasal degeneration (see “Rebel with a Cause” for more on this). Each human being has a unique DNA profile and biochemical makeup, and determining why we get sick and how best to treat us when we do is a messy, enormously complex undertaking.
The difficulties are hardly limited to the treatment of deadly diseases; even treating individual symptoms too often resembles a game of roulette. The scientists who developed non-steroidal anti-inflammatory drugs, including Cox-2 inhibitors, set out to treat chronic pain, yet post marketing, some of these drugs were found to put some patients at increased risk for heart attack or stroke. While some patients chose to sue Merck over alleged side effects from Vioxx, others are upset that it was taken off the market. Every drug has its proponents and detractors, and there is no medicine that is effective for every patient yet has never had a negative side effect in any patient.
The concept of personalized medicine — or, to use Eli Lilly President John Lechleiter’s preferred term, “targeted therapies” — offers a way forward for patients, healthcare providers and pharmaceutical manufacturers, as well as regulatory agencies, researchers, insurers and legislators. As researchers identify biomarkers that suggest who is or is not likely to respond to a given therapy, diagnostic companies are creating tests to differentiate among patients and pharma and biopharma companies are using biomarker data to inform drug development.
Speaking at Harvard Medical School’s recent Personalized Medicine Conference, Lechleiter addressed the role of drug manufacturers within the broader context of the healthcare industry’s move to an increasingly patient-focused system. He said that although the conventional wisdom is that drug companies will resist personalized medicine because they’re still focused on the blockbuster model, “our business model will accommodate personalized medicine — in fact, it may depend on it.”
In a separate interview, Lechleiter elaborates on that remark. He says Lilly executives “believe that pursuing tailored therapeutics is imperative” because:
- “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 healthcare will be more sustainable.
- “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.”
At Lilly today, fully 90% of molecules reaching the clinical development stage now have a biomarker strategy associated with them, Lechleiter notes. Aside from the benefits mentioned above, he says that on the R&D side, pursuing targeted therapies has already allowed the company “to weed out unpromising molecules earlier in the 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. Over time, we hope that… biomarker application will [result in] shorter cycle times and lower costs in drug development.”
Lilly is not the only large pharma company working on targeted therapies, but it is an “early adopter.” In addition to its internal efforts, Lilly is involved in several collaborations to advance personalized medicine and Lechleiter points out that the company “has been trying to serve as a conductor to help put others on board."
One way Lilly has done that is by “improving the transparency around our clinical trial results in pharma,” Lechleiter explains. “In 2004, our company became the first to disclose the results of all our clinical trials via 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 also improved our credibility.”
Lilly, along with Pfizer and Johnson & Johnson, is also joining with a not-for-profit health information technology group called e-Health Initiative, the Indiana Health Information Exchange and Boston’s Partners Healthcare System in a post-marketing pharmacovigilance program. “The goal is to test how safety signals can be located and understood using existing data, potentially leading to a better understanding of the risk and benefits of medicines,” according to Lilly CEO Sidney Taurel.
Through such initatives, drug companies and others involved in healthcare delivery are essentially working toward personalized medicine from both ends of the spectrum. These sorts of efforts dovetail nicely with FDA’s vision of where drug development and manufacturing should be heading in the 21st century. As it turns out, two keys to the success of both personalized medicine and quality improvement are biomarkers and access to/analysis of patient data.
Historically, access to patient data has been challenging for several reasons, including patient privacy and data security issues as well as a reluctance on the part of drug companies to share their clinical trial results. But as John Lechleiter points out, the latter has become less of a problem in the past few years. Aside from what firms such as Lilly may be doing publicly, a number of major pharma companies are making clinical trial data available to the Tucson, Ariz.-based Critical Path Institute (C-Path), an independent, nonprofit research and education institute. Established in 2005 by FDA, The University of Arizona, and SRI International (formerly the Stanford Research Institute) to “identify and prioritize the most pressing medical product development problems and the greatest opportunities for rapid improvement in public health benefits,” C-Path is also working from both the discovery and post-marketing ends of the spectrum.
Raymond Woosley, MD, PhD, C-Path president and CEO, notes that approval percentages for many types of drugs are extremely low — 5% for oncology drugs, for example. To make matters worse, at the post-marketing stage, 1-3% are taken off the market because of side effects that were not seen in clinical trials. For the sake of patients, this situation has to change, Woosley suggests.
“The regulators need to work with the regulated,” he urges. “We operate under a Memorandum of Understanding with FDA, which allows us to get FDA and EMEA to participate in collaborations along with multiple pharma companies that would otherwise be reluctant to share information for competive reasons.”
One such cooperative venture established by C-Path is the Predictive Safety Testing Consortium, which is developing data and a process to support the regulatory use of new biomarkers linked to drug safety. “Through this Consortium, we’ve brought together 185 scientists from 16 different [drug] companies, plus representatives from FDA and EMEA,” says Woosley. “We have conference calls every two weeks. Together, we’ve picked seven biomarkers for nephrotoxicity.”
Amazing results come from these collaborative efforts, which is precisely why an independent organization like C-Path is necessary, Woosley points out. “Things happen in the safety of this environment that wouldn’t happen outside. [Using the biomarkers the Consortium had identified], Merck and Novartis cross-qualified each other’s testing procedures,” he enthuses. “The resulting data looked so good that FDA created a new pathway for NDA applications, changing the process of testing for drug safety. Instead of looking at creatinine, they’ll be using BUN.”
As Woosley observes, there’s a lot of information out there that, when assembled and analyzed, can significantly improve patient outcomes by ensuring that therapies are applied in a more “personalized” manner.