With plans for a Phase III study in the first part of next year, Vivus Inc. racked up positive results from a Phase II trial testing avanafil, its oral phosphodiesterase type 5 inhibitor for erectile dysfunction, showing that up to 84 percent of the drug's doses gave men erections.
The result was statistically significant (p<0.001) vs. placebo. Vivus' stock (NASDAQ:VVUS) closed Thursday at $3.95, up 61 cents, or 18.3 percent.
The speed of avanafil's onset is "faster than anything out there," said Leland Wilson, president and CEO of Mountain View, Calif.-based Vivus, pegging the time to maximum plasma concentration at 30 minutes.
Just as important, the compound clears from the body more quickly than would-be competitors, which makes avanafil less dangerous for heart patients who might be treated with nitrates.
"Almost all guys who have erectile dysfunction have some vascular disease, so they're at more risk of having heart attacks, and the No. 1 treatment for heart attacks is still nitrates," he said.
"We showed in a previous study that in 12 hours, [avanafil] is completely eliminated from the plasma," Wilson said, whereas sildenafil, the blockbuster PDE5 inhibitor sold as Viagra by New York-based Pfizer Inc., "is still quite high at 12 hours." Side effects with Cialis (tadalifil), a PDE5 inhibitor from Bothell, Wash.-based ICOS Corp. and Eli Lilly and Co., of Indianapolis, last as long as 36 hours.
An earlier specifically designed nitrate-interaction study showed less effect on blood pressure with avanafil than sildenafil, he said, calling avanafil a refinement of currently available treatments.
In results from the most recently disclosed Phase II study, 284 patients were treated for 12 weeks with placebo or avanafil at various doses, with primary endpoints that included the percentage of erections strong enough for vaginal penetration and the percentage of erections lasting long enough for successful intercourse.
Avanafil yielded good erections in 76, 79, 80 and 84 percent of sexual attempts with doses of 50, 100, 200 and 300 mg, respectively (p<0.05), and those lasting long enough for successful intercourse were achieved on 54, 59, 62 and 64 percent of attempts, respectively (p<0.0001).
"We did not instruct our patients regarding food intake," Wilson noted. "They had no time limit since they had their last meal," nor were they prohibited from drinking alcohol. The drug was well tolerated at all doses, with no reports of visual disturbance. Headache was the most commonly recorded adverse event.
"Fourth to market is not a bad position if you're better, because the market has already been developed," Wilson told BioWorld Today. Worth about $2.5 billion, that market has "a lot of switching going on," he said. "There's really no loyalty to Viagra."
Another drug competing for a slice of the pie is Levitra (vardenafil) from Leverkusen, Germany-based Bayer AG and GlaxoSmithKline plc, of London. With all of those compounds for sale, "the regulatory roadmap [for avanafil] is very clear," Wilson said.
Vivus already markets through distributors the suppository Muse (alprostadil) for erectile dysfunction in the U.S. and overseas. In the pipeline for females is the topical alprostadil product Alista, undergoing Phase III development in sexual arousal disorder. Designed to improve sexual function by increasing blood flow to the genital tissues, Alista is being tested in patients who have had hysterectomies.
The company began enrolling Alista patients in September, and hopes to complete enrollment sometime this year. "We're about halfway through," Wilson said.
Also in development for low sexual desire in women is a spray version of testosterone using technology licensed from Acrux Ltd., of Melbourne, Australia, which has completed Phase II trials with encouraging results.
"We're working with [the FDA] right now very closely to define what is required for a Phase III program," Wilson said, adding that the company has submitted a proposal and hopes to get a special protocol assessment.
In December, Vivus started a Phase III trial of another product candidate, Evamist, a low-dose estrogen spray to treat vasomotor symptoms associated with menopause. Enrollment in that study is expected to finish this year.