Personalized Medicine: Next Big Hope or Next Big Hype?

Oncology drugs are driving the marketplace closer to the vision of personalized medicine, but major infrastructure change is still needed.

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An age of personalized medicine
is dawning. Photo from the cover
of "Medicines for You: Studying
How Your Genes Can Make a
Difference," a consumer education
brochure from NIH/NIGMS.

By Angelo De Palma, Ph.D., Contributing Editor

Recent breakthroughs in genomics have made it possible to predict, more accurately than ever before, how each patient will respond to any given drug. As a result, we hear that an age of personalized medicine is dawning, in which therapies will be tailored to groups of patients, or even individuals.

This brave new world would mean the end of the blockbuster drug model and would transform the way that medicine is practiced, and drugs are made and marketed. Armed with new testing methodologies, manufacturers would nimbly change product and production schedules in response to changing patient needs.

Are we there yet? Definitely not. Blockbusters coexist nicely with niche products today, and probably will for the next 10 to 20 years, according to Adam Bianchi, COO at Cutting Edge Information (Durham, N.C.) and companies will continue to research and develop mid-sized products and blockbusters for the near and mid-term. “Today’s pipeline drugs are the medicines that companies will be launching and marketing for the next 10 to 20 years,” he says.

Others see the blockbuster model as outdated, since even the most successful drugs don’t work in all the patients all the time. “Ninety percent of all drugs are only 50% effective,” says John Funkhouser, president of PharmaNetics, (Morrisville, N.C.), “and the top 25 drugs are anywhere from 40 to 70% effective.”

Determining the most responsive patient groups will change the structure of modern healthcare and bring sweeping changes in the way society views medicine. However, the blockbuster model will not die easily, Funkhouser believes. “Pharma is facing wide-ranging issues from consolidation, weak pipelines, longer regulatory review, fewer years of commercial intellectual property protection, generics, price pressures and political heat,” he says.

Oncology is one therapeutic area that’s moving closer to the vision of personalized medicine. A small but growing number of companies are applying a technique called “theranostics,” identifying potential responders a priori, and bundling appropriate drugs with diagnostics.

Consider Genentech’s Herceptin, for example. This breast cancer treatment originally provided only modest benefits, and some troubling side effects, for a broad patient population. However, once patients were singled out and treated who expressed the HER2/neu gene, linked to growth of more aggressive tumors, the drug’s efficacy shot up, justifying the adverse events. Bayer Diagnostics, which developed the HER2/neu diagnostic, predicts that the theranostics markets will grow by 20% per year through 2009.

As Herceptin shows, personalized medicine will create opportunities for some molecules that fail to meet traditional safety and efficacy criteria. Selecting a subgroup based on genotype can help sponsors boost efficacy into the statistically meaningful range, albeit for a smaller — sometimes much smaller — population than originally anticipated.

Individual differences justifying personalized therapies may be dramatic or subtle. In extreme cases, patients may express a gene (or protein) or not, or the gene may exist but be inactivated.

Usually, expression differences are a matter of degree. Genes make proteins, which make up the complex cascades of disease and metabolic pathways. Improperly expressed proteins can cause a drug to be completely ineffective but innocuous in one patient, ineffective but toxic in another, or safe and effective in yet another. Metabolic enzymes (and the genes coding for them), which determine a drug’s toxicity and side effects, could work so well that a drug is chopped up and excreted before it gets to work.

So personalized medicine, if it has any chance of success, relies on treating genotypes rather than phenotypes, and having the means to test for the underlying characteristic.

The manufacturing response

In response to the promises and threats of personalized therapies, pharmaceutical companies must accelerate retooling and streamlining of production lines, just as heavy and light manufacturers in other industries have done over the last twenty years. Personalized medicine means smaller batches of a wider variety of drugs. “Eventually, production managers will have to think in terms of 100 different batches of one million pills rather than one batch of 100 million pills,” notes Bianchi. Isolating process suites will become a growth industry as manufacturers will abhor overcapacity even more than they do today.

“Leaning out” operations will also be critical, as pharmaceuticals shift from the blockbuster model to personalized gene therapies and gene-specific small-molecule treatments, says Richard Chua, executive VP at the Juran Institute (Southbury, Conn.). “Companies competing in this arena will need to be lean in every sense of the word,” he notes, “including the ability to switch smoothly from one product to another.” Leaning out such processes will offer the usual benefits of streamlined, lower-variability processes, benefits which will multiply with the plant’s complexity.

At the same time pharmaceutical manufacturers will need to sharpen quality control, an activity Bianchi calls a “battleground” in the ongoing healthcare cost-control war.

It is unclear whether genomics and personalized medicine will be a centralizing or decentralizing force in pharmaceutical manufacturing. Companies will want the cost savings of mega-facilities, but also the flexibility that smaller facilities bring.

The reality for production managers is that they will have to accommodate both cost-consciousness and rapid change. While large drug firms will probably always rely on blockbusters to some extent, the eventual emergence of medicines tailored for niche groups will require manufacturing facilities that are adept at handling smaller fill orders and that can switch rapidly between brands, says Dr. Frederick Cohen, president and founder of Crownstone (Bensalem, Pa.), a healthcare consultancy group.

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