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Powerful new medications or something more sinister?

Posted by shutah on July 2, 2007

CAMBRIDGE, Massachusetts:

 By Andrew Pollack

Can an antipsychotic drug from the 1950s be paired with a 1980s antibiotic to shrink 21st-century tumors? Might an anticlotting drug help a steroid relieve arthritis? How about a cholesterol treatment and a pain reliever teaming up to tame diabetes?

Alexis Borisy, the pharmaceutical industry’s master matchmaker, is betting they can. And if he is right, he may have found a cheap and quick way to develop a new cornucopia of medicines.

Borisy is the 35-year-old co-founder and chief executive of CombinatoRx, a biotechnology company dedicated to the proposition that two old generic drugs can together make a powerful new medicine, often for an entirely different disease.

It is too early to tell if Borisy will succeed and, indeed, one of his company’s drugs failed in a clinical trial last week.

But with drug makers big and small struggling to fill their product pipelines, other biotechnology companies are also betting that pairing old drugs can be a better business than inventing new ones from scratch – which can take years and cost hundreds of millions of dollars, with no guarantee of success.

For example, Pozen, based in Chapel Hill, North Carolina, is developing combination drugs in partnerships with the pharmaceutical giants GlaxoSmithKline and AstraZeneca.

Orexigen Therapeutics of San Diego, recently went public based on the prospects for two combination drugs it is developing to treat obesity. And privately held Celator Pharmaceuticals of Princeton, New Jersey, has raised more than $40 million from venture capitalists to combine old cancer drugs in a new way.

“We think if we prove this concept clinically we have an almost unlimited pipeline,” said Andrew Janoff, the chief executive of Celator.

Helping propel the trend is the growing supply of drugs that have lost patent protection, providing a lode of material to test for newfound potential.

Information technology also plays a key role for CombinatoRx (which is pronounced com-bin-a-TOR-ics, as in the mathematics field that deals with combinations). The company relies on the latest robotic drug-screening technology and software to test several thousand pairs of medicines a day.

At its laboratory here, researchers and robots systematically pair about 2,000 generic drugs with one another, with two million different combinations possible.

Each is tested on human cells. If a drug pair inhibits the cells’ production of inflammatory proteins, for example, that might be reason to explore whether the combination might work against arthritis.

Borisy describes it as a “dumb, brute-force, empirical approach” that assumes current knowledge of disease is too limited to predict in advance what combinations might work. The company does, though, give priority to testing pairs it believes have the best chance of working.

Eight of the company’s randomly arranged marriages, including drugs for cancer, arthritis and diabetes, have moved into clinical trials – an unusually high number for a company that is only seven years old.

Besides being quicker or cheaper to develop than single new drugs, combinations might also be more effective. Doctors routinely use two or more drugs to treat people with cancer, heart disease, HIV infection and other diseases.

But only more recently have pharmaceutical companies decided to do the combination themselves as a way to increase their profit.

Successful combination drugs already on the market include Advair from GlaxoSmithKline, which pairs two asthma drugs, and Vytorin, which combines cholesterol-lowering drugs from Merck and Schering-Plough that work in different ways.

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