BIG PHARMA'S DISMAL DEVELOPMENT FORECAST IS HARDLY a secret. Drugs worth some $20 billion are going off patent in 2006, and most observers see too few drug candidates emerging
to replace them. In the face of new generic competition, says Barbara Ryan, pharmaceuticals analyst at Deutsche Bank, "US-based
companies don't really appear to have enough new drug candidates coming on-stream to allow these companies to grow."
In vivo animal imaging is one of many technologies Gene Logic uses to discover how drug candidates react in different biological
What companies do have is an enormous backlog of stalled drug compounds, or "dead drugs," as they are sometimes called. Nine
of 10 drugs that enter human trials are "discontinued," as the industry delicately puts it, sometimes for safety reasons,
but often after they fail to reach just one or two crucial clinical endpoints. Uncounted thousands of such compounds have
been shelved at pharmaceutical companies large and small. Most never return to the clinic.
Companies that are willing to talk about these drugs at all say they would love to repurpose them—to look for new clinical
targets, or even to chemically modify compounds in order to reduce safety hazards or increase efficacy. But, to judge by company
practices, most drug developers see shelving inactive drug candidates as a solid business decision. Ignoring the once promising
compounds frees up R&D resources for drugs that are still in the pipeline.
At Gene Logic—a Gaithersburg, Maryland company best known for its fee-for-service toxicogenomics screening services and drug
analyses using human-tissue databases—these discontinued drugs spell opportunity. Not only are they the foundation of a new
business unit at Gene Logic, such failed compounds may become the cornerstone of a new approach to R&D as the industry confronts
its latest productivity crisis. Most discontinued compounds are dumped after failing tests for a single indication. Such quick
clinical exits might have made sense when chemistry ruled drug development, and repurposing a drug would have meant adding
or removing a crucial chemical group on the molecule. But shelving candidates early is a poor drug-development strategy in
the biological age, Gene Logic contends. Instead of modifying stalled compounds, the company systematically tests them for
activity against hundreds of different diseases. And if they get a "hit," the stalled compound could be headed back to clinical
trials within a year.
"We let the compound tell us what it is," says Mark Gessler, Gene Logic's CEO. "If the compound is active, we can find out
what it does." Using genomics and other technologies, scientists at Gene Logic have developed a battery of tests to check
the activity of compounds against bio-markers and gene targets for more than 400 diseases. No molecule is chemically altered
to increase its chances of hitting a therapeutic target—whether the clinical trial's original one or a new one. No drug is
re-engineered. Instead, the company seeks to discover, with systematic biological screens and assays, how—if at all—a drug
interacts with a broad range of biological systems. At Gene Logic, this is known as "interrogating" a compound. Literally
asking it how it reacts biologically.
The idea is to do systematically in the laboratory for many compounds what happens serendipitously during clinical trials
and practice for a few. Viagra (sildenafil), Botox (botulinum), and even thalidomide, for instance, have become successful
drugs when they proved effective for indications their creators did not anticipate. Why shouldn't unanticipated applications
rescue compounds that never made it out of the clinic?