Old drugs, new life

Developers hope it could sell nearly as well as Viagra, the Pfizer Inc. pill for erectile dysfunction. While those blue pills affect a man's blood vessels, dapoxetine changes the level of the chemical serotonin in the brain and nervous system that controls orgasm.

"Viagra works on the plumbing. This works on the wiring," said Karl B. Thor, chief scientific officer of Dynogen Pharmaceuticals Inc. in Boston. Thor previously worked at Pharmaceutical Product Development Inc., or PPD, a Wilmington, N.C., company now developing dapoxetine, a leftover compound from an unsuccessful effort to develop a depression therapy similar to Prozac.

The story of how dapoxetine was rescued from the dumpster of abandoned therapies is becoming a tale often told in the biotechnology industry. The idea isn't new: Faced with huge costs and long timelines to develop drugs, companies are keen to find new uses for old compounds that have already gone through some phases of testing for safety and efficacy -- and thus in theory face less work to bring to market.

Serono Inc. of Rockland, for instance, developed a human growth hormone for children but discovered the same drug could help AIDS patients regain body mass. Merck & Co. Inc.'s Propecia hair-loss drug began under the name Proscar, for shrinking the prostate gland. And GlaxoSmithKline PLC also sells its Wellbutrin SR depression drug under the name Zyban, to help quit smoking.

The latest trend, however, is that companies are beginning to find novel uses of compounds that somehow failed the initial goals of their developers or that have not progressed.

For instance, closely held Combinatorx of Boston conducts large numbers of tests to find new uses for existing compounds. Another local company pursuing a similar strategy is Xanthus Life Sciences Inc. of Cambridge, which is trying to find better ways to use drugs like the anticancer drug Amonafide, developed by the National Cancer Institute in the mid-1990s. It was found to be too toxic for some patients.

Xanthus aims to develop tests to find the ideal amount of medicine for each patient -- to personalize the dosage, in other words. It also aims to develop and sell the drug itself.

"They already had drugs that had been through a lot of previous testing," said Mark P. Carthy, a partner at venture-capital firm Oxford Bioscience Partners in Boston, which has invested in Xanthus. "They can get a faster start, and get to the end phase quicker."

Oxford is also an investor in Dynogen, which said Dec. 22 that it agreed to license from Mitsubishi Pharma Corp. a drug that Dynogen hopes will be useful for treating irritable bowel syndrome.

Mitsubishi had originally pursued the drug to treat depression, but didn't see effective use in trials. Dynogen had already filed for a patent on the drug, in keeping with its strategy of finding novel uses for drugs that have been abandoned or are under development for other purposes.

"A lot of the drugs we file patents on aren't going anywhere, so we're giving them new life," said Lee R. Brettman, Dynogen's chief executive.

The story of dapoxetine shows the strategy's potential. The drug was first noticed by scientists at Eli Lilly and Co., the Indianapolis pharmaceutical giant.

Lilly produces the antidepression drug Prozac, the best-known of a class of drugs known as selective serotonin reuptake inhibitors, or SSRIs, which can produce sexual side effects. Dapoxetine is also in that class, but according to Dynogen's Thor it was set aside as a depression therapy partly because it has a short duration of action, meaning patients must take the pills several times a day for a lasting effect.

That could be an advantage for a pill meant for sex, Thor realized. Previously a researcher at Lilly, Thor heard of the work on dapoxetine and later took the right to work on that drug and others he called "fallow assets" to GenuPro, a former unit of PPD, the North Carolina drug developer.

In turn, PPD licensed the drug as a sexual therapy to Alza Corp., purchased by Johnson & Johnson in 2001. Johnson & Johnson disclosed its work on the drug several months ago; it will pay PPD an undisclosed royalty stream if dapoxetine is eventually approved for sale.

A Johnson & Johnson spokeswoman said the company won't say more about the trial results to date or forecast revenue.

On Dec. 18 PPD announced it had agreed to pay $65 million to Lilly in return for the cancellation of Lilly's interest in dapoxetine. On a conference call with investors, PPD chief executive Fred Eshelman said the company will also pay Lilly royalties of 5 percent of annual sales of more than $800 million, and that it expects peak annual sales of $750 million.

The companies wouldn't say when the drug might be ready for sale, but one guess is mid-2006, according to Ira D. Sharlip, an assistant clinical professor of urology at the University of California at San Francisco and a spokesman for the American Urological Association.

Sharlip said he is working as a consultant to several companies, including Johnson & Johnson, all trying to develop similar treatments. Word of the drugs has led to much discussion in medical circles, since the condition is the most common form of sexual dysfunction in men under the age of 45, he said.

If one of the drugs were approved, Sharlip said, "I think it would command a lot of attention."

Ross Kerber can be reached at kerber@globe.com.