Washington Editor

Lilly ICOS LLC's proposed drug for erectile dysfunction apparently gives men the ability to achieve an erection some 24 to 36 hours after taking it. Comparatively, Pfizer Inc.'s blockbuster drug Viagra offers only an eight-hour window.

But similar to Viagra, nitrate patients are strictly prohibited from taking the Lilly ICOS drug called Cialis, said Raymond Rosen, a Cialis study author and director of the program in human sexuality at the University of Medicine and Dentistry of New Jersey, and professor of psychiatry at the Robert Wood Johnson Medical School in Piscataway, N.J.

"We've participated in a number of studies and we have not had any safety problems with Cialis," Rosen told BioWorld Today. "But it has the same contraindication as a Viagra patient taking nitrate - it can have a potentially dangerous interaction with nitrate. Aside from that, we have not seen any cardiovascular safety problems. All the data I'm aware of shows this product to be very safe from any point of view."

Lilly ICOS was among several entities that presented promising data on drugs designed to treat erectile dysfunction (ED) at the 97th Annual Meeting of the America Urological Association in Orlando, Fla. (Lilly ICOS is a joint venture between ICOS Corp., of Bothell, Wash., and Eli Lilly and Co., of Indianapolis, that is developing Cialis.)

Also at the meeting, Bayer Corp. and its partner, GlaxoSmithKline plc, presented positive efficacy data on their ED drug referred to as vardenafil; and New York-based Pfizer Inc. released good results of a study of Viagra in black men.

But the Phase III study released by Lilly ICOS is particularly significant because it indicates that Cialis (tadalafil), an oral PDE5 inhibitor, remains active in the body longer than its competition, Viagra. Lilly ICOS filed a Cialis new drug application last June based on positive results from another Phase III study in which 85 percent of participating men experienced improved erections. (See BioWorld Today, June 29, 2001.)

In its approvable letter issued on Cialis late in April, the FDA requested confirmatory clinical pharmacology studies as well as a resolution to labeling issues and outstanding manufacturing deficiencies at Lilly. Company officials expect the U.S. launch in 2003. (See BioWorld Today, May 1, 2002.)

Data from the Phase III trial released at the meeting Saturday were collected from a study of 348 men with mild-to-severe ED who were randomly assigned to receive Cialis 20 mg (n=175) or placebo (n=173) over approximately eight weeks. Patients were instructed to attempt intercourse with their partners on four specific occasions: on two occasions at 24 hours after dosing and on two occasions at 36 hours after dosing. The primary endpoint was the percentage of successful sexual intercourse attempts, according to a statement released by Lilly ICOS.

"We found that the drug was active in 60 percent of the patients up to 36 hours," Rosen said. "The drug doesn't automatically produce an erection. It is only effective if you are in a situation of sexual stimulation."

In most patients, Rosen said, activity begins 30 minutes after taking the drug. No more than one pill should be taken in a 24-hour period, but it can be taken two or three times in a week.

Cialis was statistically superior to placebo in secondary efficacy measures, including ability to penetrate, satisfaction with hardness of erection and overall satisfaction.

The most commonly reported (greater than 5 percent) treatment-emergent side effects in the study were headache, flushing and upset stomach. Fewer than 2 percent of patients taking Cialis or placebo discontinued the study due to side effects. There were no treatment-emergent serious adverse events reported.

Data collected from large-scale Phase III clinical trials involving 1,328 men with ED show that the overall incidence of cardiovascular side effects - including flushing, dizziness, hypertension and feeling faint or fainting - in both placebo and Cialis-treated patients was not statistically significant, the company said.

Meanwhile, Bayer, of Leverkusen, Germany, and GlaxoSmithKline, of London, released data Saturday from two Phase III clinical trials that enrolled about 1,400 men. According to the companies, a significant proportion of men reported that vardenafil treatment improved their erectile function regardless of whether their condition was organic, psychogenic or a mixed cause, compared to placebo.

Also, patients with ED and co-existing hypertension, hyperlipidemia or diabetes reported a marked improvement in erectile function with vardenafil, a PDE5 inhibitor. The vardenafil NDA was filed about three months after Cialis.

When additional information was requested by the FDA on the Cialis application, analysts began speculating whether a similar request would be made of Bayer - or whether Bayer would reach the market first.

Finally, Pfizer released safety and efficacy data from a study of Viagra (sildenafil citrate) in black men suffering from ED. A statement released by Pfizer said about eight out of 10 participating patients reported improvement in their erectile function and ability to have sexual intercourse after taking Viagra for six weeks.

In that study of 246 black men, patients were randomly given Viagra or placebo for six weeks, at which point they were given the choice to switch to the alternate treatment for another six weeks. At week six, a significantly larger percentage of Viagra-treated patients reported "improved erections" and "improved ability to have sexual intercourse" (79 percent and 81 percent) compared with placebo-treated patients (38 percent and 36 percent). Additionally, patient satisfaction was greater in the Viagra-treated group than in the placebo group, Pfizer said.

Lilly's stock (NYSE:LLY) closed Tuesday at $63.97, up 16 cents, while ICOS' stock (NASDAQ:ICOS) closed at $24.16, up 93 cents.

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