Lilly ICOS LLC: First Presentation of Large-Scale Integrated Analysis of Phase III Data on Cialis -- tadalafil -- Shows Consistent Effect in Men With Erectile Dysfunction.

Business Editors and Health/Medical Writers

ROME--(BW HealthWire)--Oct. 2, 2001

New Study Shows Cialis Absorption Not Affected by Food Intake

The first presentation of a large-scale integrated analysis of Phase III data on Cialis(TM) (tadalafil), a new oral treatment for erectile dysfunction (ED) being developed by Lilly ICOS LLC, shows a consistent response to the investigational treatment. Eighty-one percent of patients treated with 20 mg Cialis (N=165) reported improved erections.(1) This analysis, taken from studies of 972 men with ED (711 Cialis, 261 placebo), and other new research - including a study that shows Cialis's absorption was not decreased by food intake(2) - were presented today at the 4th Congress of the European Society for Sexual and Impotence Research (ESSIR) in Rome.

"With each new data analysis, we continue to see consistent and robust scientific evidence that Cialis has an attractive profile," said Charles Beasley, M.D., medical director, Eli Lilly and Company. "The many findings from these Phase III analyses suggest Cialis has the potential to be a valuable treatment for a large number of men who have ED, regardless of severity. Cialis has other attributes that may also be clinically important."

Pharmacokinetic Analyses: Key Findings

Several studies were conducted to evaluate Cialis absorption by the body. Pharmacokinetic studies are important because they can identify differences in drug absorption and elimination in the body between various patient populations. These studies investigated, among other characteristics, the impact of age, diabetes, renal function, and liver function on the pharmacokinetics of Cialis(TM). There were no clinically significant differences in extent of drug exposure among these diverse groups. In addition, Cialis's absorption was not decreased by food intake.(3)

"These findings suggest that dosing for Cialis should be simple and uncomplicated, which is important from a health care professional standpoint," said Harmut Porst, associate professor of the urological department of the medical university in Bonn, Germany, and secretary general of the ESSIR. "From a patient's point of view, it is the absence of food effect that I find most interesting. These data suggest that a man can have a normal, romantic dinner with his partner without diminishing the effect of Cialis."

Integrated Phase III Analysis - Key Findings From General and

Diabetes Populations

The integrated Phase III analysis included randomized, placebo-controlled studies involving 972 men with ED of various causes and severity. Men were treated with Cialis (ranging up to 20 mg) or placebo for 12 weeks. Improved erections, as assessed by the Global Assessment Questionnaire (GAQ), were reported by 81 percent of patients taking 20 mg Cialis (35 percent placebo).(4)

The Phase III integrated analysis showed Cialis improved erections in 76 percent of the subset of men with diabetes taking a 20 mg dose(5). Diabetes-related ED is often more difficult to treat than ED caused by other factors. ED is a common complication of diabetes, affecting between 27 and 75 percent of men with the disease.(6) The World Health Organization estimates 151 million people worldwide have diabetes.(7)

In the Phase III studies, participants were instructed to take study medication at the time of their choosing prior to sexual activity, with no more than one dose daily. No instructions were given with regard to food or alcohol consumption and time of dosing.

Cialis Period of Responsiveness - Key Findings

Two separate studies, presented in Europe for the first time, showed Cialis works for up to 24 hours and as early as 16 minutes after taking the pill(8). In the first study, 61 men with mild-to- severe ED were randomized to take Cialis(TM) or placebo and underwent RigiScan(R) (device for measuring firmness and duration of erections) evaluations during exposure to visual sexual stimulation. Men taking Cialis experienced significantly more success in improvement of erectile function than men in the placebo group, even when evaluated 24 hours after dosing. In the second study, designed to measure the drug's onset, 223 men took Cialis or placebo and used a stopwatch to record the elapsed time until they achieved an erection sufficient for intercourse. The ability to achieve an erection (with sexual stimulation) was statistically superior in the group taking Cialis 20 mg, compared with the placebo group, at 16 minutes after dosing, and the majority of men taking Cialis were able to respond within 30 minutes.

"This period of responsiveness may be an important attribute for emerging ED treatments, as it may enable a man and his partner to have sex whenever they choose within a 24-hour period," Professor Porst said.

Side Effects 

Throughout the Phase III trials, Cialis was well tolerated, with generally mild-to-moderate side effects that diminished in frequency with continued treatment. The most commonly reported side effects throughout the Phase III trials were headache, upset stomach, backache, muscle aches, flushing and nasal congestion. The discontinuation rate due to side effects in these trials was comparable to that with placebo.

Cialis is currently under review for marketing approval by the European Agency for the Evaluation of Medicinal Products (EMEA) and the US Food and Drug Administration (FDA).

Erectile dysfunction is defined as the consistent inability to attain and maintain an erection sufficient for sexual intercourse. It affects an estimated 152 million men and their partners worldwide with many cases caused by physical conditions, including cardiovascular disease and diabetes.(9) In Europe, approximately 31 million men suffer from ED.(10)

About Lilly ICOS

Lilly ICOS LLC, a joint venture between ICOS Corporation (NASDAQ:ICOS) and Eli Lilly and Company (NYSE:LLY), is developing Cialis(TM), which is currently under investigation for the treatment of sexual dysfunction.

Eli Lilly and Company, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.

ICOS is a product-driven company that has expertise in both protein-based and small molecule therapeutics. ICOS combines its capabilities in molecular, cellular and structural biology, high throughput drug screening, medicinal chemistry and gene expression profiling to develop highly innovative products with significant commercial potential. ICOS applies its integrated approach to specific target areas where it has expertise. ICOS believes its strategy of targeting multiple therapeutic areas by developing drugs that act through distinct molecular mechanisms increases its chances of successfully developing commercial products.

This press release contains forward-looking statements about the potential of the investigational compound Cialis (tadalafil) in treating male erectile dysfunction that reflect management's current beliefs. However, as with any pharmaceutical under development, there are risks and uncertainties in the process of development and regulatory review. There are no guarantees that future clinical trials will confirm the preliminary results reported in this release or that the product will receive regulatory approvals or prove to be commercially successful. For further discussion of these and other risks and uncertainties, see the U.S. Securities and Exchange Commission filings of ICOS and Lilly.

(1) Symposium, "Expanding treatment options for male impotence."

4th Congress of the European Society for Sexual and Impotence

Research. October 2, 2001.

(2) Patterson, B et al. "The effect of intrinsic and extrinsic 

factors on the pharmacokinetic properties of tadalafil

(IC351)." Poster presentation at the 4th Congress of the

European Society for Sexual and Impotence Research. Poster

presented 08.00-09.00 October 3, 2001.

(3) Ibid.

(4) CME symposium, "Expanding treatment options for male

impotence." 4th Congress of the European Society for Sexual

and Impotence Research. October 2, 2001.

(5) Ibid.

(6) Guay A. Treatment of erection dysfunction in men with

diabetes. Diabetes Spectrum 1998; 11: 2

(7) International Diabetes Federation. Diabetes Atlas 2000.

(8) Padma-Nathan, H. "Tadalafil (IC351) provides prompt response

and extended period of responsiveness for the treatment of men

with ED." Poster presentation at the 4th Congress of the

European Society for Sexual and Impotence Research. Poster

presented 08.00-09.00 October 1, 2001.

(9) Aytac et al. The Likely Worldwide Increase in Erectile

Dysfunction Between 1995 and 2025 and Some Possible Policy

Consequences. BJU International. 1999; 84:50-56.

(10) Ibid.