Tar Heel Tattler - May 2005

Dead-end drugs show side effects
By Edward Martin

GlaxoSmithKline might have thought it was immune. The drug maker recently played bystander as several Research Triangle Park neighbors took a licking. First, tests indicated Inspire Pharmaceuticals’ new ocular lubricant was no more a sight for sore eyes than a placebo. Then Biogen Idec, which made an acclaimed multiple sclerosis drug, revealed that three users had died of liver damage. In Durham, Icagen quit testing an experimental epilepsy drug because of safety concerns.

But only a few days after Biogen stopped sales of Tysabri, the federal Food and Drug Administration halted GSK’s testing of its code-named 699 multiple sclerosis drug because it worked on a similar principle. “It was chemically different, but the FDA hit the pause button to figure out what happened to Tysabri,” GSK spokeswoman Gaile Renegar says.

Traditionally, for every 10,000 chemical compounds tested, only one is approved for sale. The odds may be getting even longer. Experts blame heightened awareness of drug safety, a proliferation of new compounds and other factors for a rash of canceled or delayed drug launches.

Tar Heel drug makers could use a dose of the antidepressant Zoloft. The Triangle feels the pain more than most drug centers. It has giants like 6,000-employee GSK, which has one of its North American headquarters in RTP, as well as smaller companies such as Inspire, which typically work on early-stage drugs when risks of failure are highest. Chapel Hill-based Pozen recently had a migraine drug approved — but only after two others failed in 2003 and 2004. Cases such as those and Inspire’s diquafosol, which the company had hoped the FDA would accept as a dry-eye treatment, show the hurdles new drugs face.

Inspire applied for permission to test diquafosol in June 2003, says Jenny Kobin, senior director of investor relations. Tests proceeded, and the company hoped to market it this year. But in early 2004, the FDA ordered more tests. The verdict was that diquafosol was no more effective than a saline solution. Inspire stock dropped 45% the day of the FDA announcement.

But not all dead-end drugs are dead. Kobin says Inspire hopes to get FDA approval to sell its dry-eye drug for corneal wounds, such as those left by laser surgery. Sometimes Plan B works out OK, too: Scientists at New York-based Pfizer Pharmaceuticals were testing a drug called sildenafil in the early 1990s for use in treating the heart condition angina when they discovered unexpected side effects. Viagra sales topped $1.5 billion in 2004.