National Editor

Money might not buy love but, as Pfizer Inc.'s blockbuster Viagra proved, it can do wonders for sexual capability in men who have the wherewithal to pay for the magic blue pill. Talk about "hard cash."

A survey by Decision Resources Inc. in March of 75 primary care physicians and 21 managed-care pharmacy directors predicted Viagra (sildenafil citrate) would remain the top seller in ED. (See BioWorld Financial Watch, May 12, 2003.)

The reason cited was cost. The price is what drives most patients away from Viagra, said doctors who responded to the survey, and 67 percent of pharmacy directors told pollsters they would add one of the competing drugs if it were priced 50 percent below Viagra. Almost half of the pharmacy directors said they would do it if the alternative drug cost 40 percent less.

But pricing trends, plus new information in the form of prescription numbers and data from head-to-head comparison studies, suggest factors other than money might strongly affect the ED race, which has yet to gain full steam in the U.S. At this point, price is "completely off the table," said Christopher Raymond, analyst with Robert W. Baird & Co.

In August, the FDA approved Levitra (vardenafil) from Bayer AG and GlaxoSmithKline plc. The drug, which, similar to Viagra, inhibits the enzyme phosphodiesterase type 5 (PDE5), is said to take effect in 60 minutes or less, with one recent study showing a 16-minute onset in some men (although the label instructs patients to take Levitra 60 minutes before sex). Viagra is said to act in 45 minutes to 90 minutes.

Levitra should not be taken by men using alpha-blockers, which means patients with benign prostatic hyperplasia, among others. "Pfizer has cautionary language [for such patients]," Raymond noted, "but Levitra is absolutely contraindicated. That's a disadvantage."

Coming down the pike is Cialis (tadalifil), yet another PDE5 inhibitor for ED, this one a product of the joint venture between ICOS Corp. and Eli Lilly and Co., called Lilly ICOS LLC, for which the FDA accepted a new drug application in July. Already on the market in Europe, Cialis is expected to win approval in the U.S. this year or early next. The drug gained marketing clearance in Canada last month.

Cialis' main selling point is that it works for 24 hours to 36 hours. It has benefits at the starting gate, too, with some men reporting activity at 16 minutes after dosing, as with Levitra. Most, though, say the drug takes about 30 minutes to work.

In other words, Cialis seems to have a quick onset and much longer efficacy, plus a strong safety profile, Raymond said.

ICOS Lilly says that, from Cialis' launch in February in Europe to June, the drug captured a "significant" share of ED sales in terms of units among the three PDE5 inhibitors as bought by pharmacies from wholesalers in several European Union countries.

"They've priced it absolutely on par with Viagra," Raymond said, putting Cialis in the same ballpark as Levitra as well. "That tells me they're being aggressive." The same is expected in the U.S., he said.

German Study Tests Drug Trio Against One Another

During June, Cialis had 30 percent of unit share in Germany, followed by 27 percent in France, and 21 percent in Italy. In the UK, Cialis has gained 13 percent share of units. In countries where Lilly has rights to market Cialis, the product had 33 percent of unit share in Australia and 20 percent in Brazil.

In the U.S., where the battle so far is limited to Viagra and Levitra, IMS Health found Levitra, priced in Viagra's range, picked up about half of ED prescriptions in newly diagnosed patients during its first month of sales, but Viagra still holds the lion's share of the market in the U.S.

Raymond, who subscribes to another prescription-tracking service, was skeptical about the IMS numbers. In any case, he said, it's "a phenomenon you see in this category." When Viagra was approved, it showed a "not completely linear upward trajectory, but pretty darn close. After a few months it almost went in the opposite direction," and then leveled out, he said.

Levitra is likely to be helped by data from the first clinical study to evaluate it against men for whom Viagra doesn't work. Bayer and GSK said last week that such men in the study were three times more likely to complete sexual intercourse with Levitra than with a placebo. Results were to be presented Oct. 11-12 at the fall meeting of the Sexual Medicine Society of North America in Denver.

At the same meeting, Lilly ICOS was expected to disclose data showing 62 percent of men who had undergone bilateral nerve-sparing radical retropubic prostatectomy for prostate cancer benefited from Cialis. About half of such men are said to report ED starting about 18 months after the surgery.

More data from ED research are due in November from the European Society of Sexual Medicine in Istanbul, Turkey.

An ongoing study by Hartmut Porst, urologist and professor at the University of Bonn in Germany, pits all three PDE5 inhibitors against each other for the first time ever. Each patient will try every drug, although so far 226 patients were evaluable for a comparison between only Viagra and Cialis.

Results: 66 percent preferred Cialis, 21 percent Viagra, and 13 percent had no preference. Main reasons given for the Cialis preference were duration of action (89 percent), onset of action (53 percent) and fewer side effects (47 percent).

In the trial, 82 percent of the patients had been using Viagra for more than two years. The rest had never been treated with a PDE5 inhibitor, so they were given at least six doses of Viagra first, and then given Cialis, after which they completed a standard test called the International Index of Erectile Function, along with a preference questionnaire.

Those preliminary outcomes of the trial, which will enroll 900 patients, were offered at the 55th Congress of the German Urological Society in Hamburg, Germany, late last month, and will be repeated at the Istanbul event. Porst's podium session for the upcoming Istanbul meeting is titled, "What patients prefer and why: Sildenafil vs. Tadalafil in a real-life, at-home setting."

Cialis Ads Likely To Target Sex Partners, Too

Another study by the same doctor did manage to test all three drugs, one after the other, in 150 patients with a mean age of 58 years, of whom 126 were long-term Viagra users and only 24 were treatment-na ve for ED.

Results, also to be presented in Istanbul: Those who preferred Cialis at the 10-mg dose again led the pack (45 percent), with Levitra next (30 percent) and Viagra - which most had been using - last (13 percent). The "no preference" group (12 percent) was mostly non-responders.

"The overwhelming majority of the patients prefer the two new drugs, with [Cialis] being ahead, due to its long duration of action," Porst concluded.

Raymond said the studies sound anecdotal, but he wasn't surprised by the finding that patients liked Cialis best.

"More than any other pharmaceutical product, this is a consumer product, so the marketing proposition is inherently different," he said.

"This is squishy marketing logic, but I think Lilly ICOS has caught on to a key component in decision making that has been missed by Pfizer, and that's the [sexual] partner," Raymond said, pointing to "a fairly large number of recalcitrant men" who might not ask their doctors for ED drugs "without a little prodding."

Even Cialis' gentler-sounding name seems geared at least partly to females, he said, and he expects "a different tack" to be taken by Lilly ICOS in its advertising, which is likely to include an appeal to women "instead of an in-your-face, male-dominated Mike Ditka campaign."

News surfaced in July that Lilly ICOS had hired football hero "Iron" Mike Ditka, former coach of the New Orleans Saints, as spokesman for Levitra.

Furthermore, space has been made for Cialis to occupy.

"There are examples across the landscape of pharmaceuticals where you have an incumbent that essentially paved the road," Raymond said. "Prozac created the SSRI market and then Zoloft was launched a couple of years later with a better sexual side effect."

Brand loyalty is hardly a factor in pharmaceuticals, either. "This isn't like Ford and Chevy, and even that isn't what it used to be," he said.

Will there be more PDE5 inhibitors?

"My sense is, sure, there is room for that," Raymond said. "I would liken this [Cialis] opportunity to Aranesp [darbepoetin alfa]," the second generation of the red-blood-cell booster Epogen (epoeitin alfa), from Amgen Inc., he added.

"In Europe especially, you've got a couple of erythropoietins, and probably a couple more in a few years," Raymond said, but Aranesp rules the roost.

"Viagra's not going to zero - I wouldn't argue that at all," he said. Cialis, however, will be a "category-transforming product," Raymond predicted, and not all the value has yet been built into ICOS' stock, which was trading late last week in the $40 range.

"I still hear a number of pushbacks" among investors doubtful whether ICOS will win approval this year, as many expect and as Raymond believes it will.

"Unless there's a complete meltdown in biotech, I believe this stock will have a 5' in front of it after [Cialis'] approval," he said.