By Matthew Willett

ICOS Corp.'s first Phase III study of its PDE5 inhibitor for treatment of erectile dysfunction showed efficacy among the majority of a population of men with diabetes-related ED.

In the 216-patient, randomized, placebo-controlled trial, 64 percent of treated patients talking the compound, called Cialis by ICOS, reported improved erections. Cialis, the company said, significantly improved sexual function compared to placebo across the board of endpoints regardless of patient age, duration or severity of ED or diabetes.

ICOS' director of investor relations, Lacy Fitzpatrick, said the response and improvement data the trial yielded is exceptionally high in the diabetes-related ED population.

"The 64 percent response rate we've seen is considered high," Fitzpatrick told BioWorld Today. "We're reporting in this trial just in diabetic men, but in the broader population the improvement rates have been between 81 [percent] and 88 percent."

She said several Phase III trials are under way, and added that the compound also is under evaluation for treatment of female sexual dysfunction. Its market could encompass 70 million men in North America and Europe alone, and 152 million men worldwide.

"We're on schedule to file the new drug application in the second half of this year," Fitzpatrick said. "We're conducting Phase III trials, and some of them are concluding, and we're preparing to present additional Phase III data throughout the year."

She said the company will present Phase III data at the European Association of Urology Meeting this week and at the American Urology Association meeting in Anaheim, Calif., in June.

Cialis inhibits PDE5, or phosphodiesterase type 5, an enzyme in smooth muscle that controls the level of cyclic GMP (guanylic acid), much like Pfizer Inc.'s ED treatment Viagra. Inhibiting PDE5 increases the level of cyclic GMP, allowing blood vessels to dilate.

ICOS' director of clinical research, Albert Yu, said the drug inhibits the flow of blood coming out of the penis to maintain an erection. Its action, he agreed, is similar to Viagra in mechanism.

"It has the same mechanism of action in terms of inhibiting the PDE5 enzyme," Yu said. "The difference is that, first, the chemical structure is different, and second, there's a difference in terms of how selective it is against other phosphodiesterases, a family of related enzymes with about a dozen members. Cialis is more selective against the phosphodiesterase in the eye, for example, about 600 times more selective. Viagra is not that selective."

And, he said, the company is evaluating the drug for potential cardiovascular interactions.

"The danger, the risk, has to do with the potential interaction with nitrates, a family of medications some coronary artery disease patients take," Yu said. "If a patient is taking nitrates, Viagra is contraindicated, and that's something we're looking at in our trials in terms of potential effects."

The compound is under development through a joint venture with Eli Lilly & Co., of Indianapolis, named Lilly ICOS LLC.

That venture was formed from the collaboration the companies entered for Cialis development in 1998 that included milestone payments and $75 million in operations funding to ICOS from Lilly. (See BioWorld Today, Oct. 2, 1998.)

The companies will share marketing rights for the drug upon commercialization in North America and Europe through the joint venture. Lilly will maintain rights in all other markets.

ICOS' stock (NASDAQ:ICOS) fell $3 Friday to close at $41.875. n