An unknown quantity

In discussing personalized medicine, it’s helpful to triage the conversation into what we know, what we think we know, and what we can only guess at. And it is that final subject that keeps us up at night either with night sweats or anticipating the opportunities.

What we know
Personalized medicine, the use of genetic or other biomarkers to improve the safety and effectiveness of medications and improve health outcomes of patients through more efficiently targeted risk stratification and tailored treatments, will inevitably transform the practice of medicine (and the marketing of medical products) just as the harnessing of monoclonal antibodies opened new therapeutic opportunities 15 years ago.

Phase one of this medical transformation is being played out as newly marketed tests are helping predict whether existing medications will be effective and safe for patient “A” and what will be his optimal dose to treat his condition or disease. There are now some 2,000 genetics tests on the market, and today some 10 percent of medications contain pharmacogenomic information.

Some easy examples: the anti-coagulant Coumadin is a life-preserving medicine for patients at risk of deep vein thrombosis or atrial fibrillation. However, too large a dose puts the patient at risk of serious bleeding and too little may have an inadequate therapeutic effect and the patient may have a stroke. But now doctors can monitor  precisely  pro-thrombin time to determine how effectively the blood thinning medication is working and when to adjust the dose. Move over guess-work, hello predictability.

In the oncology arena, new therapies such as endo-thelial growth factors Vectibix and Erbitux help prolong the lives of many patients with colorectal cancer. But these drugs don’t work their wonders on all patients and, in fact, the European regulatory authorities denied Vectibix market authorization based on its limited usefulness in the general colorectal cancer population. However, scientists have recently learned that a mutation of the KRAS protein sharply increases resistance to the drug and diminishes its effectiveness. Available genetic testing can help identify and exclude the 35 percent of patients with this mutation, allowing us to treat more patients successfully. Europe may reconsider its decision based on this finding.

What we think we know
While testing to determine effectiveness and safety in individual patients is the “here and now”of personalized medicines, its real promise, we believe, is the development of medications specifically targeting an individual’s unique genetic profile. The wondrous prospect is that we can target precisely genetic abnormalities that cause illness in each individual patient, making drugs that are snipers’ rifles rather than scatterguns. Instead of treating hypertension, a condition with many antecedents, we will tell Mr A that his high blood pressure is the result of a genetic mutation resulting in the production of too much rennin and that medication XYZ can ameliorate this defect.

The old concept of the $5bn blockbuster therapy may evaporate, but in its stead will be a verdant marketplace with many, many products targeting specific genomic markers. Insurance companies and the government won’t have to cross their fingers and hope that paying for an expensive biotechnology-derived therapy isn’t a fool’s errand. This is the dream of “version 2.1” personalized medicine.

What we don’t know
Sounds great so far. But it’s what we don’t know that causes the night sweats for drug developers, marketers and PRs working in biotech. Here are some of the unknowns.

Are we getting ahead of ourselves?
The public’s imagination with new “curative” technologies has traditionally exceeded industry’s ability to deliver. Ten years ago, the “first draft” map of the human genome was announced with great fanfare by The National Institutes of Health. This schematic of what makes us “us” was portrayed as the blueprint for identifying the causes of diseases and their treatments. However, despite the unquestioned importance of this discovery, diagnostics and certainly treatments resulting from the blueprint have been slow in coming. As Harold Varmus, MD, incoming director of the National Cancer Institute said in The New York Times, “genomics is a way of doing science, not medicine”.

Communicators will have to be extraordinarily cautious about promising more from personalized medicine than can be realistically delivered. As always, the best way to inform the public about personalized medicine is to manage expectations and avoid the temptation to suggest that such-and-such a treatment will “revolutionize medicine” or “cure” this-and-that disease.

Will the public accept the concept?
While the public generally grasps new science as a panacea, they can be skeptical of innovations.

Twenty years ago a small but vocal minority criticized biotechnology as a dangerous form of alchemy and a potentially harmful intrusion on Mother Nature. More recently, fresh evidence points to entrenched behaviors as the norm. An article in the July 2010 issue of Health Affairs,  entitled Evidence That Consumers Are Skeptical about Evidence-Based Health Care, suggests that few consumers understood terms such as “medical evidence” or “quality guidelines”. Most people surveyed believed that more care meant better care. These incorrect assumptions may be hurdles in controlling spending.

For PRs working with biopharma firms, it is essential to assure the public that personalized medicine does not mean relieving one’s doctor of decision-making responsibilities.

Thoughtful and well-trained medical and science journalists understand the nuances between hyping medications and broadcasting realistic goals for personalized medicine. However, news resources are contracting at an alarming rate. Will reporters new to the science beat appreciate the importance of keeping the story balanced? We can hope they will, but better than hoping is helping new science reporters keep articles in perspective.

“Not one disease, but many?”
For a 100 years we have bucketed disease states broadly: Mr Jones has diabetes; Ms Smith has high blood pressure and Mrs Cruz has breast cancer. It was a relatively simple system of classification based on the symptoms and organ structures affected.

As we learn more about the waltz-like interplay between genes, we are discovering that the old classifications are not that simple. Our genetic exploration is leading to the conclusion there may be numerous causes of a single disease. For instance, insulin-dependent diabetes  may be predicated by one of several abnormalities in the genes located on the HLA portion of one’s chromosomes. Depending on the genes involved, different forms of diabetes may present. Other big-ticket diseases such as irritable bowel disease, breast cancer and hypertension may have multiple origins.

While the variations in genetic defects may only be interesting to molecular biologists today, this could change radically in the future as doctors make patients with unique genetic patterns aware of contributing environmental factors, dietary needs and unique therapies. Disease educators won’t have the luxury of talking only about “the” disease.

Genetic discrimination?
A pervasive fear has been that genetic information will lead to discrimination or favoritism based on one’s genome. Thanks to the Genetic Information Nondiscrimination Act of 2008, insurance companies and employers cannot use genetic information as the basis for denying insurance or a livelihood. The Act, signed by President Bush, was the result of a decade-long bipartisan effort to protect citizens against the threat of genetic “self-incrimination”.

But will this act hold? What the courts affirm one year can be made non-operative the next. As genetic information becomes more widely available and cheaper, the wall dividing the individuals’ privacy and the curiosity of employers becomes less imposing. Sooner or later these issues will be joined on the public battlefield. How we communicate the issues involved will tax the limits of great communicators.

The Author
Michael Durand, Managing Director, Resolute Communications