Researchers presented encouraging preliminary results last month from a Phase Two trial of vardenafil, a new treatment for erectile dysfunction being developed by the Bayer Corporation. The study showed that vardenafil was safe and effective in treating erectile problems in older men.

At a meeting of the American Geriatric Society in Chicago, Christopher P. Steidle, MD, detailed findings from a 199-patient, randomized, placebo-controlled study designed largely to determine the proper dose of vardenafil. All of the men in this study had mild-to-severe erectile dysfunction that had persisted for at least the six months leading up to the study.

Steidle's presentation focused on a subpopulation of men who were 65 years of age or older. The performance of vardenafil in senior men is of special interest. The likelihood of erectile dysfunction increases with age, as does the likelihood of diminished cardiovascular health or other diseases and conditions that limit or prohibit the use of Viagra.

In the 65+ group, vardenafil was most effective at a dose of 20 mg, compared with doses of 5 mg or 10 mg. In comments reported by Reuters Health, Steidle declared the drug safe for men over 65 with erectile dysfunction, and cited his study's finding of only mild-to-moderate side effects, including nausea, back pain, and a stuffy nose--effects, he added, that are typical of this type of drug.

At the annual meeting of the European Association of Urology, earlier this year (April 2001), Irwin Goldstein, MD, presented results from a 580-patient, multinational, randomized, placebo-controlled dose-ranging study of vardenafil in men aged 21 to 70 years. The drug was said to improve erections in up to 80% of men and to improve their ability to complete sexual intercourse with ejaculation. The most frequently reported adverse events were said to be generally mild and included headache, flushing, rhinitis (inflammation of nasal membranes), and dyspepsia (stomach upsets).

What's a PDE-5 inhibitor and why do we need another one?

In terms of how it works, vardenafil falls into the category of PDE-5 inhibitor, as do Viagra and several other drugs now under study. PDE-5 (phosphodiesterase type 5) is an enzyme, a chemical messenger in the body, that tells a man's erection to subside. PDE-5 is a good thing--no one wants a permanent erection--but in men with erectile dysfunction, temporarily "silencing" PDE-5 with an inhibitor, like Viagra, can help restore erectile capacity and normal sexual function.

There are other PDEs besides PDE-5. These are found in the eyes, brain, heart, and kidneys and are involved in a number of non-reproductive functions. Viagra's weakness, according to its competitors, is that it lacks specificity for PDE-5--that it inhibits the action of other PDEs at nongenital sites and produces side effects. Among the signal side effects of Viagra, for example, is seeing a bluish tinge to objects or having temporary difficulty distinguishing blues and greens. These ophthalmic effects are thought to be due to Viagra's partial inhibition of PDE-6, which is found in the retina.

Vardenafil is one of a new generation of PDE-5 inhibitors that are supposed to distinguish themselves from Viagra by having greater specificity for PDE-5 and causing fewer side effects, thus being easier for patients to tolerate. Confirmation of a superior side-effects profile, however, will require randomized clinical comparisons directly with Viagra in a sizeable number of men. Its comparative effectiveness will also have to be put to the same test.

How soon to market?

Bayer says it will file for FDA approval to market vardenafil in the U.S. by the end of 2001. The company hopes FDA review will be completed by the latter half of 2002.

Hard on the heels of vardenafil, however, come a handful of "new generation" PDE-5 inhibitors claiming improved specificity compared with Viagra. If their safety and effectiveness pan out, maybe the competition will give consumers some meaningful therapeutic options and lower prices.