Topical antifungal may help toenails

Trial to show whether liquid medication reaches infection in nail bed

August 25, 2006|By Regina Nuzzo | Regina Nuzzo,LOS ANGELES TIMES

When fungus invaded her toenails 10 years ago, Ruth Carsch of San Francisco didn't care too much at first. Her nails became "thick and fat and yellow," says the 61-year-old information specialist, but she could always hide that behind colorful nail polish.

What she really minded, she says, was how the nail plates grew so thick from the infection that they squashed the toes beneath. "My toes are much fatter than they used to be. My feet are wider," Carsch says. "It seems to have deformed my toes."

Her podiatrist suggested topical creams, but often they couldn't reach the skin-loving fungus underneath the nails. "Or they could take my toenails out," Carsch says. "I wasn't ready for that one." She refuses to take either of the two antifungal pills available, she says, because her sister-in-law had a dangerous drug interaction after taking one of them.

Carsch has instead signed up to help test a new topical antifungal treatment. The hope is that the liquid medication, manufactured by Anacor Pharmaceuticals of Palo Alto, Calif., can penetrate toenails, reaching infections on the nail bed and eliminating fungus.

More than 35 million adults in the United States have at least one nail -- usually a toenail -- that is infected with fungus, a condition known as onychomycosis or tinea unguium. Infection risk goes up with age; between 25 percent and 40 percent of people older than 40 are affected, according to the American Academy of Dermatology.

Infected nails rarely get better without treatment, says Raza Aly, professor of dermatology at the University of California, San Francisco. According to some industry estimates, toenail fungus sufferers worldwide spend about $300 million on topical treatments and about $2 billion on oral antifungals each year.

Still, fungal nail infections appear to be on the rise in the United States, Aly says. This includes a growing number of women, whose infection rates have traditionally lagged behind men's. It's still unclear why more women are seeking treatment, but Aly suspects that new footwear fashions are to blame. "Women are catching up to men. Now they're also wearing tennis shoes and other occlusive shoes for several hours a day," he says.

For many sufferers, an infected toenail is nothing more than an embarrassing eyesore. But for others, it could lead to more dangerous conditions, says Dr. Richard Scher, a professor of dermatology at Columbia University in New York. In patients with diabetes or with circulatory or immune system problems, for example, a fungal infection can open the door to a bacterial infection in the skin or veins in the legs -- a condition more difficult to treat, especially in these patients.

Existing toenail fungus treatments aren't perfect, Scher says. Two antifungal pills, terbinafine and itraconazole, work well in most people but have been known in rare situations to cause serious liver problems such as hepatitis. Plus, some patients, such as Carsch, prefer to avoid oral treatments or cannot take them because of drug interactions.

Only one topical treatment, ciclopirox, is approved by the U.S. Food and Drug Administration for treating nail fungus. In a lotion, the drug works well for fungal skin infections -- athlete's foot, for example -- but in a lacquer, its efficacy for a complete cure is only 5.5 percent to 8.5 percent, Scher says.

Now researchers at Anacor hope their new drug can go where others can't. "We set about finding a molecule that not only acted against the organisms that cause onychomycosis, but that also penetrated the nail and nail bed," says Dr. Karl Beutner, chief medical officer at Anacor. The new drug -- a fungicidal, rather than a fungistatic like many current treatments -- is designed to kill fungus, not just slow its growth. Called AN2690 for now, it works by shutting down the fungus' protein synthesis process, Beutner says.

The drug's small molecules seem to absorb easily into the water-rich environment of toenails, Beutner says. In the lab, researchers applied AN2690 every day for two weeks to detached cadaver fingernails. They found that 16 percent of the solution seeped all the way through the nails -- 200 times the amount that a ciclopirox solution managed under the same circumstances.

Two Phase 2 clinical trials of AN2690 are under way in the United States and Mexico. Researchers are looking to see whether patients treated with the drug will grow at least 5 millimeters of fungus-free nail over six months. Halfway through the study, preliminary results suggest that 13 out of 24 patients are on track to meet that criteria, showing at least 2.5 millimeters of clear toenail growth, Beutner says.

Other companies are also working to develop topical antifungal treatments. Novartis AG, in Basel, Switzerland, is designing clinical trials in the United States and Europe for a new topical treatment containing terbinafine, the same antifungal in its oral medication. And in January, MediQuest Therapeutics of Seattle started recruiting for a Phase 2 clinical trial to test terbinafine and naftifine -- an antifungal commonly used to treat athlete's foot -- in a new type of gel designed to effectively penetrate the nail.

Carsch realizes that compared with other potential health problems, her thick yellow toenails aren't so bad. The infection isn't painful, and she hasn't had any complications, she says. Still, it would be nice to have her old toes back.

"I can't wear certain shoes," she says. "I can't wear cute little strappy sandals."

Regina Nuzzo wrote this article for the Los Angeles Times.

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