Palatin Technologies Inc. reported positive data from a Phase IIb trial with PT-141, an erectile dysfunction drug that has not only proved effective but also - thanks to a different mechanism of action - gets around the potential cardiovascular problems with existing therapies.
"It's a little na ve to say that you'll replace sildenafil," said Carl Spana, president and CEO of Cranbury, N.J.-based Palatin. "Our objective is to be the only non-PDE5 inhibitor, first-line therapy."
The study results were presented Saturday at the 8th annual Leadership Conference on Sexual, Cardiovascular and Metabolic Syndrome-Related Therapies in Los Angeles.
However, Wall Street punished Palatin's stock (NYSE:PTN), which closed Monday at $3.45, down 85 cents or 19.8 percent, after dipping as low as $3.25.
"I've been talking to people all day," Spana said. "I think there was some confusion in the press release as to what we said we were doing, and you had some jittery guys out there."
Some investors "didn't quite understand this was a dose-ranging study, and I think we could have been clearer on the efficacy side," he told BioWorld Today, adding that "all doses showed very good efficacy," with many "p" values "in the 0.001 or better" range.
The placebo-controlled, randomized, double-blind, parallel-group study enrolled at 21 sites 271 men with mild to moderate and severe ED. All were patients who already had been shown responsive to sildenafil citrate, the phosphodiesterase type-5 inhibitor otherwise known as Viagra, New York-based Pfizer Inc.'s blockbuster ED drug.
Included in the "at-home" study were smokers and men with conditions such as diabetes, hypertension and hyperlipidemia - all conditions associated with ED. Researchers compared participants' baseline score on the International Index of Erectile Function-Erectile Function domain questionnaire before and after one month of treatment, which was randomized to placebo, 5 mg, 10 mg, 15 mg or 20 mg of PT-141, a melanocortin agonist.
Nasally administered PT-141 achieved both clinical and statistical significance (p<0.05 or better) in restoring erectile dysfunction at the 10 mg and higher doses relative to placebo, as shown by IIEF-EF domain scores, which was the primary efficacy endpoint.
It also restored normal erectile function, defined as a score of 26 or more on the EF domain of the IIEF questionnaire, at all four PT-141 doses relative to placebo, and improved the quality of erections, determined by the Global Assessment Questionnaire score, which Palatin described as "highly significant" for all four doses of PT-141, relative to placebo.
"The quality of erections seems to be superior to what they're getting on Viagra," Spana said. "They actually can feel the drug on board and working and that seems to be an important point. It reduces their anxiety in approaching their partner."
That, combined with "a very clean cardiovascular safety profile," an onset time of 20 minutes to 30 minutes and a duration of action from eight hours to 12 hours, should make PT-141 a strong choice for men with ED, Spana said.
The company expects no interaction problems with nitrates or alpha-blockers, he added, though the FDA likely will want more drug interaction studies.
"We have done the only one required by the agency, which is an alcohol interaction study," Spana said. "There was no effect on PT-141 with alcohol, nor did it exacerbate the hypotension that occurs with alcohol." Tests also have been done with Viagra non-responders, and the results were "very favorable," he said.
All doses of PT-141 in the Phase IIb study proved safe, with no reports of hypotension or syncope at any dose level. The 5-mg and 10-mg doses were well tolerated, the most common adverse events at those doses being mild to moderate in intensity, including bad aftertaste, facial flushing, nausea, post-nasal drip, fatigue and headache.
Of the 271 patients randomized into the study, about 12 percent quit due to adverse events. Discontinuations due to gastrointestinal adverse events were limited almost exclusively to patients taking the 15-mg and 20-mg doses. Patients who took multiple 15-mg and 20-mg doses of PT-141 tolerated the drug well.
About 70 percent of patients said PT-141 was as effective as sildenafil or more so, with the quality of erection said to be comparable or superior by 83 percent.
Another Phase IIb study is in the offing, Spana said. An end-of-Phase II meeting with the FDA regarding Phase III plans is expected in the "third or fourth quarter" of next year, he said, with approval possible in mid-to-late 2007, assuming the drug stays on course.
Three PDE5 inhibitors for ED are available worldwide: Viagra; Levitra (vardenafil), from Bayer AG, of Leverkusen, Germany, and GlaxoSmithKline plc, of London; and Cialis (taladafil) from ICOS Corp., of Bothell, Wash., and Eli Lilly and Co., of Indianapolis. Viagra and Levitra are approved in Europe and the U.S.; Cialis is available only in Europe, with U.S. clearance expected later this year.
Despite onset and duration times that differ somewhat, the drugs are priced about the same - which makes sense, Spana said.
"In the U.S. marketplace, probably 70 percent of these guys are paying out of pocket," he said. "It would not be good precedent to undercut pricing."
Whether Palatin might charge more "will depend on results of pivotal trials" and other research yet to be done, Spana said. Tests with PT-141 in Viagra non-responders have yielded "very favorable" results, and patients generally "see clear benefits they would pay more for," he added.
PT-141 grew out of work done at the University of Arizona in Tucson, Spana said. Palatin in-licensed the compound and "we found out what the metabolite was," he said. "It turned out the metabolite was more effective."