Wednesday, June 17, 2009

A Smart Drug Company? Holy Crap!

This week's Business Week cover story features Novartis, apparently the one drug company not as dumb as Detroit. The good news is that smart management there may provide a new model for badly needed new drug development. The bad news is that none of these drugs are likely to be psychiatric meds.

Novartis is the one drug company headed by a medical doctor, Don Vasella (pictured here). The others are dominated by lawyers and accountants and marketers who fail to appreciate science and who have forgotten who their true customers are. According to Business Week:

"Most big drugmakers shower their research and development funds on diseases such as cancer or depression, where huge potential markets beckon despite a deficit of scientific understanding. In recent years this approach has led to high rates of failure when drugs are tested in clinical trials."

In contrast, seven years ago, Novartis embarked on a policy of pushing drugs through testing and development only if they were backed by proven science. It didn't matter that the particular diseases the drugs treated were rare. In the words of Dr Vasella: "If you are guided purely by financial estimates and not the science, you end up wasting time and money."

Novartis' Gleevec was initially approved for a rare blood cancer that strikes just a few thousand people a year, but has since proved effective against six other diseases. Last year, the drug pulled in $3.7 billion in sales.

The idea is that although there are 24,000 genes in the human genome, there are only a few dozen pathways that are shared by virtually all diseases. The trick is to track down all the links in a pathway, then locate the key signals that switch genes on and off.

In the development phase at Novartis is a drug to treat a rare inflammatory disorder called Muckle-Wells syndrome, involving a single gene variation that may be implicated in other illnesses. Thus, the rare diseases may shed light on a host of other illnesses and hold the key to future drug discovery.

Here's where the drug industry's blockbuster/me-too mentality has left us, according to Business Week:

Experts say drug companies have exhausted the easy targets. With patents on many older blockbusters starting to expire, the industry is poised to lose an estimated $140 billion in sales to generic competition over the next five years. Those revenue sources must be replaced.

Despite multibillion-dollar research budgets, none of the top companies has a wealth of promising compounds in its development pipeline. The industry also faces regulators more vigilant than ever about safety, and health insurers starting to balk at covering costly drugs that bring only modest benefits.

Dr Vasella shook things up when he moved Novartis' main global research operation from Basel, Switzerland to Cambridge, MA, and got a Harvard cardiologist to run it, with a brief to turn things upside down. Under the new order, scientists stared calling the shots rather than executives in sales and marketing.

The men and women in suits fought back hard, but ultimately more than a thousand sales and marketing execs were purged and medically trained scientists brought on board.

Here's the catch: Our current scientific understanding of mental illness would not meet Novartis' rigorous standards for green-lighting new drug development. According to its 2008 Annual Report: "Diseases affecting the brain and central nervous system pose exceptional hurdles in drug discovery."

All our current psychiatric meds are the result of serendipitous discovery, based on old technologies. They get some of the people somewhat better some of the time, and we have no idea why. The drug industry made vast sums of money essentially putting old pills in new bottles. That era is just about over.

The new era would involve finding the precise illness pathways that cause specific mental illness symptoms and figuring out which gene variations are involved. Forget about a treatment for all of depression. Rather, it might be more productive to uncover the underlying mechanisms to, say, lack of motivation. Maybe only a small percentage of depressions involve lack of motivation. But maybe such a drug would get a lot of these people a lot better a lot of the time.

Maybe, also, this motivation drug would help with other diseases and conditions that involve lack of motivation, such as various neurological ills. Maybe also various fatigue ills, and maybe even the flat affect symptoms of schizophrenia.

And maybe the best way of testing the drug would be to first try it on some really rare disease that only two people in the world know anything about, and then branch out.

Would your typical drug company be interested? No way.

Might Novartis be interested? You bet, assuming the science is sound. A ray of hope ...

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It's Official: Pharma is Dead to Us

Pharma and Biotech: No Practical Solution Yet

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