Genentech Debacle Highlights Larger Problems with Pharmaceutical Research

When an FDA advisory committee decided yesterday that the blockbuster colon and lung cancer drug Avastin is not a suitable treatment for breast tumors, the stock price of the drugmaker Genentech dropped dramatically. During the ensuing media frenzy, Arlene Weintraub at Business Week had the wisdom to take a step back and examine the scientific challenges facing the pharmaceutical industry.

At the beginning of her article, Weintraub hit upon some of the core problems of many large drug companies and used Genentech as a counterexample.

As the drug industry grapples with patent expirations and a chronic lack of exciting drugs in the pipeline, Levinson (Genentech CEO) faces a unique challenge—living up to his own track record. Genentech gave birth to the biotech industry in 1976, exploiting a new technique to produce protein-based drugs from cloned genes. Levinson started out as a cancer researcher at the company in 1980 and moved quickly up the ladder by espousing a radical set of management principles: Stay focused on the science. Tune out Wall Street’s insistence on short-term profits. And leap at new drug opportunities "that other people think stink."

That paragraph is so rich that it deserves some further elaboration.

Monkey See, Monkey Do

Pharmaceutical companies are very reluctant to test drugs that work in new and exciting ways. They often jump on the same bandwagon. Medications that follow in the footsteps of an existing blockbuster are often called "me too" drugs. For instance, the painkiller Vioxx, which was recalled after serious safety concerns, is one of several drugs that target the inflammation-causing protein COX II. A painfully similar drug, Bextra, was also removed from the market for the same reasons.

The biological buttons that drugs push are called targets. A report published in Nature Reviews Drug Discovery last year highlighted the shocking lack of variety. Even though there are over one thousand drugs on the market, their counterparts are numbered in the hundreds. Further illustrating just how many copycats there are, a poster by the same authors [pdf] showed that only 186 human proteins are the targets of drugs that can be taken orally.

Rushing Drugs to Market

The business folks in drug companies have a hard time waiting around for their scientists to find the perfect cure. By forcing researchers to work on a rigid timetable, managers often force scientists into making bad decisions.

Understanding Human Variation

The one size fits all approach does not work in medicine. But for years, pharmaceutical companies have failed to acknowledge that a drug which works well for one patient may make another terribly ill. 

The breast cancer drug Herceptin is the greatest exception. It only works on about 30 percent of patients, but fortunately there is a test to see which ones will respond favorably. That sort of treatment, testing patients before giving them a drug, is called personalized medicine.

Later in her article, Weintraub explained that Genentech is investing heavily in that area. She says that the company keeps track of the first people to receive their experimental drugs and looks for biological signposts that will predict how well others will respond.

To better match patients with drugs, Levinson took the odd step of hiring away five autoimmune specialists from a single lab at the University of Minnesota last year. They are experts in searching for "biomarkers," molecular signals that reveal the unique makeup of each patient’s disease. While the pool of patients for each personalized drug is small, such treatments can be lucrative.

Genentech held a press conference yesterday. An archived webcast is available on their site. Link