Washington Editor

Lilly ICOS LLC's erectile dysfunction candidate, Cialis, is on track for FDA action this year, company officials said Wednesday, announcing that the agency accepted the new drug application as complete following submission of additional pharmacology and other data.

If Cialis makes it to market early next year, it likely will provide men suffering from erectile dysfunction a third option in treatment, behind New York-based Pfizer Inc.'s Viagra and Levitra, an ED drug made by Bayer AG, of Leverkusen, Germany, and GlaxoSmithKline plc, of London. Levitra is slightly ahead of Cialis in the U.S. regulatory race, with an FDA action date scheduled later this summer, Bill Tanner, managing director of Leerink Swann & Co. in Boston, told BioWorld Today.

Viagra has enjoyed worldwide exclusivity since 1998 and last year raked in close to $2 billion.

All three products are PDE5 inhibitors, but Cialis offers men a little something different - time. Unlike Viagra, which produces results for up to six hours, Cialis works for 24 hours to 36 hours and basically can be taken by any man who is not taking nitrate. After taking Cialis, some men report activity at 16 minutes, although the majority note activity at 30 minutes.

Tanner believes Cialis will be a billion-dollar drug.

Lilly ICOS, a joint venture formed by ICOS Corp., of Bothell, Wash., and Eli Lilly & Co., of Indianapolis, submitted its new drug application for Cialis two years ago. In April 2002, the agency reported that Cialis' approvability was contingent upon additional confirmatory clinical pharmacology studies, labeling negotiations and manufacturing inspections. (See BioWorld Today, May 1, 2002, and June 29, 2001.)

Responses to the FDA's concerns were submitted during the second quarter, Lacy Fitzpatrick, ICOS' director, investor relations, told BioWorld Today. While she said Lilly ICOS conducted the pharmacology studies, Fitzpatrick would not disclose the nature of the studies, nor would she discuss specifics surrounding labeling or manufacturing issues. Furthermore, she would not disclose the date the submission was filed, the date the FDA accepted it or the anticipated Prescription Drug User Fee Act action date. (Federal law requires the FDA to act on drug and biologics applications within a certain time period.)

Cialis works by inhibiting PDE5, or phosphodiesterase type 5, an enzyme in smooth muscle that controls the level of cyclic GMP (guanylic acid). Inhibiting PDE5 increases the level of cyclic GMP, allowing blood vessels to dilate.

Last fall Pfizer filed a lawsuit against Lilly ICOS, Bayer and GlaxoSmithKline in the U.S. District Court in Delaware claiming that their ED products infringe on the Viagra patent. The case is pending. (See BioWorld Today, Oct. 24, 2002.)

Fitzpatrick said the difference between Cialis and other ED drugs is apparent in the labeling carried in countries where the product already is marketed.

"In Europe the Cialis label notes that it may be effective up to 24 hours, but in Australia the label says 36 hours. We think patients will value that characteristic," Fitzpatrick said.

While a longer half-life potentially is positive in terms of dosing frequency, it could be problematic in relation to drug interactions, Tanner said.

Another difference in the drugs is the relationship to food. Fitzpatrick said the European label notes that Cialis can be taken without regard to food. But for Viagra, food has a different impact.

"Depending on what you eat, the efficacy of Viagra can vary," Tanner said. "If you eat a high-fat meal, the drug appears not to be that effective. That does not appear to be the case for Cialis."

Cialis has been marketed in Europe since February and so far the PDE5 inhibitor appears to be capturing 20 percent to 30 percent of the market, Fitzpatrick said.

Tanner's estimate, at least for Germany, was a little higher, at 30 percent for Cialis and low double digits for Levitra. "The market share hasn't grown because you can envision that there would be a percentage of patients that would be dissatisfied with Viagra that would be sort of low-hanging fruit. Once they've switched to a drug that's new, then the incremental margin growth might come fairly slow," he said.

The venture between Lilly and ICOS is a 50-50 deal in North America and Europe. In other territories, including Australia, Asia, Africa and South America, Lilly has rights and is required to pay royalties to the joint venture.

ICOS received $15 million in milestones on entering Phase III and submitting the FDA application. Fitzpatrick said other payments are built into the deal, but have not been disclosed.

ICOS' stock (NASDAQ:ICOS) rose $1.89 Wednesday to close at $39.56.