Data from a proof-of-concept trial came up short for Vivus Inc., which disclosed that its PDE5 inhibitor did not improve outcomes for men with premature ejaculation.

The Mountain View, Calif.-based company studied the ability of VI-0162 (TA-1790) to increase time to ejaculation, relative to placebo and another phosphodiesterase type 5 (PDE5) inhibitor, Viagra (sildenafil, from Pfizer Inc.). Data from the double-blinded study showed that neither drug fulfilled expectations - Vivus said previous studies suggested that inhibition of PDE5 was associated with increased time to ejaculation.

Its shares (NASDAQ:VVUS) fell 56 cents on the news Tuesday, or 11.1 percent, to close at $4.49. But Richard Walliser, the company's chief financial officer, said the results did not signal a clear decision to halt development of the drug in that indication.

"We have to evaluate the trial a little more thoroughly to determine whether or not there is any reason to continue," he told BioWorld Today. "There were three studies done by doctors independent of Vivus using Viagra, and they all reported positive results. But in our trial with Viagra as a baseline and our TA-1790, we didn't see results. We need to evaluate whether there was any efficacy or not."

Premature ejaculation is a secondary indication for the compound, though, which is being developed primarily for the erectile dysfunction market. Vivus said previously reported Phase I data point to VI-0162's improved efficacy over other PDE5 inhibitors in that indication.

Findings showed that peak efficacy response to its drug was comparable or greater than that observed with Viagra, based on RigiScan device measurements that determined penile rigidity in association with visual sexual stimulation. Also, the peak penile response with VI-0162 occurred 20 to 40 minutes after administration, compared to peak response with Viagra occurring 60 to 120 minutes later. Data also showed that 89 percent (24 of 27) of VI-0162-treated patients achieved penile rigidity of better than 60 percent within 20 to 40 minutes, compared to 46 percent (12 of 26) Viagra-treated patients in the same timeframe.

In the erectile dysfunction market, Vivus is positioning the drug as a competitor to Viagra, Cialis (tadalafil, from Eli Lilly and Co. and ICOS Corp.) and Levitra (vardenafil, from Bayer AG).

"If we can prove an advantage over the other three, which we appear to be able to do, then there is room in the marketplace for a fourth drug," Walliser said, adding that the company is planning to begin an at-home Phase II study in parallel with a trial to determine its interaction with nitrates as well as other pharmacokinetic studies. "So far, the indications are that we're safer, work faster and are as effective if not more so than anything we have tested it against."

But Vivus is not abandoning the premature ejaculation market entirely. The company said a controlled clinical trial has shown that VI-0134, an oral, on-demand psychotropic compound, was able to significantly increase the ejaculatory latency period.

"We did demonstrate efficacy in a proof-of-concept study a couple of years ago, so we're also going to evaluate whether we want to go back to that drug or do some more trials," Walliser said. "We believe premature ejaculation is a very large, unsatisfied market, and we don't want to walk away from it until we know [VI-0162] simply didn't work. If that's the case, we'll probably visit our other one."

He said there are no FDA-approved pharmaceutical products specific to the condition. Instead, patients numb the problem with psychotropic drugs or creams designed to have a deadening effect. The company has a patent on the use of VI-0134 in combination with PDE5 inhibitors.

Beyond the oral male sexual dysfunction drugs, Vivus is studying a formulation of alprostadil called Alista, which is applied to female genitalia to treat female sexual arousal disorder. Alprostadil is a synthetic version of prostaglandin E1, a naturally occurring vasodilating agent.

Vivus also is studying VI-0162 in combination with its already marketed, transurethrally delivered alprostadil product.

Just more than a month ago, the company raised $17.5 million after completing a private placement of about 4.4 million common shares. Prior to the sale, Vivus reported a cash position of about $30 million through March 31. Following the offering, the company had about 37.5 million shares outstanding. (See BioWorld Today, May 29, 2003.)