For reasons that might be as much socio-economic as medical, female sexual arousal disorder (FSAD) has been overlooked in favor of the lucrative market for erectile dysfunction therapies such as the pioneering phosphodiesterase type-5 inhibitor Viagra from Pfizer Inc.
But FSAD is real. It's believed to afflict about 40 percent of the overall population, especially those who are postmenopausal or who have undergone hysterectomies.
"One complaint is lack of desire and the other is lack of arousal" - two distinct problems requiring different approaches, said Leland Wilson, president and CEO of Vivus Inc., which last week started a Phase III trial with its drug Alista for FSAD.
Alista, to be tested at 40 sites, is a proprietary formulation of alprostadil, a synthetic version of the vasodilator prostaglandin E1 (PGE1), which is applied locally to female genitalia to increase blood flow. The treatment deploys the same active ingredient as Vivus' therapy for ED, called Muse, which brings in about $20 million per year for the company, Wilson told BioWorld Financial Watch.
"It's real easy to put on," he said of Alista, comparing it to lotion. "You don't even have to touch it with your hands." Instead, the treatment is squeezed out of its packaging onto an applicator.
There hasn't been much available for FSAD, other than over-the-counter (or over-the-Internet) potions such as Vigel, a topical gel that contains the amino acid L-arginine, which boosts nitric oxide in the body, thus triggering the manufacture of cyclic guanosine monophosphate, an expander of blood vessels. An ad states Vigel "also contains peppermint, which gives women a pleasant tingle." Other cream formulations include ginseng, menthol and methyl nicotinate.
In April 2000, the FDA cleared for marketing a device for FSAD from UroMetrics Inc. Called Eros Therapy, it's a small, handheld contraption that involves a soft plastic cup placed over the clitoris. When the device is activated, it creates a gentle vacuum to increase blood flow.
Vivus is looking at something a bit more systemic with Alista, which targets arousal. The company also has a drug for the desire side of the FSAD equation - a testosterone spray expected to enter Phase III trials in the first quarter of next year. A Phase II study is concluding.
The booming market for ED drugs, especially PDE5 inhibitors, is hardly being overlooked by Vivus, which is turning some of the conventional marketing wisdom on its head with avanafil, formerly known as TA-1790, licensed in January 2001 from the Japanese firm Tanabe Seiyaku Co. Ltd.
Watchers of the ED space might expect something like a next-generation Cialis (tadalafil), possibly a drug that lasts even longer in the body than the compound from Lilly ICOS LLC, which boasts a 36-hour span of efficacy. But Vivus is going the other direction, boasting that avanafil acts quickly but also is eliminated from the body much faster than other PDE5 inhibitors. The reason is the drug class's dreaded interaction with nitrates - often given in the emergency room to treat heart attacks - which can be fatal.
ED in the first place can be an indicator of cardiovascular disease, Wilson noted, especially in the middle-aged to older population. "Those small arterials [in the penis] are starting to get clogged for one reason or another," he said, and that can be an indication that larger passageways are blocked as well.
Cialis, sometimes called the "weekend drug," allows for spontaneity rather than timed dosing like the other PDE5 inhibitors. The quicker onset of avanafil could make near-spontaneity possible, too, while avoiding the possible drawbacks of the compound lingering in the body.
"If you look at reality, people take the drug [near the moment] when they want to have sex," Wilson said. "End-use failures occur because they can't wait long enough." So avanafil seeks to provide the same benefits as Cialis, or almost, without the disadvantages.
"We've shown in well-controlled studies that we're faster than Viagra," Wilson said, allowing that the research into such areas can be challenging. "We also think it potentially has a better safety profile."
Another PDE5 inhibitor is Levitra (vardenafil) from Bayer AG and GlaxoSmithKline plc, said to take effect in 60 minutes or less, with one study showing a 16-minute onset in some men (although the label instructs patients to take Levitra 60 minutes before sex). Viagra acts in 45 minutes to 90 minutes.
"One of the confusing areas [when studying ED drugs] is that some patients who take the medication and try to have sex earlier than they should are able to," Wilson said. "But they probably didn't need the drug in the first place." Controlled studies test plasma levels of the drug.
As many predicted, recreational use of the PDE5 inhibitors and their readily available generic versions manufactured overseas has been growing - although not all of the compounds are suitable for all men.
Levitra, for example, has a major hitch: it's not to be taken by men using alpha-blockers, which means patients with the rather common condition of benign prostatic hyperplasia, among others. Pfizer also has cautionary language on its label about alpha-blockers, but they're outright contra-indicated with Levitra.
Proponents of therapies for female sexual dysfunction might say it's almost inevitable that a story about the subject would turn into a discussion of male problems, but Wilson noted they go together - and followers of Vivus "argue back and forth which of these [markets] will be bigger, but they'll both be huge."
RBC Capital Markets last week reiterated its "outperform" rating for Vivus, which RBC assigned to the firm when it began coverage in July.