Healthy Skepticism Library item: 8754

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Publication type: news

May J.
The race is on to develop a magic bullet for bedroom problems like premature ejaculation and, for women, low sexual arousal
Star-Ledger (New Jersey) 2007 Feb 25
http://www.nj.com/starledger/stories/index.ssf?/base/business-5/1172381961166670.xml&coll=1&thispage=1

Full text:

More than a decade ago, scientists at Eli Lilly developed an antidepressant called dapoxetine that proved to be a flop.

It left the body too quickly to be effective for its intended purpose, but a former Lilly researcher who specialized in gastro-urological disease thought it might work on something else: premature ejaculation, the most common male sexual disorder. “I knew Lilly had dapoxetine sitting on the shelf,” said Karl Thor, the researcher. “It had been in man. It looked safe in preliminary trials.”

Dapoxetine appeared to be that rare thing, a drug that could potentially surpass Pfizer’s Viagra, the little blue pill for erectile dysfunction that pulled in $1.66 billion last year, thanks to relentless advertising.

Johnson & Johnson ultimately acquired rights to the drug, which in clinical trials was found to delay orgasm some three to four times longer in men who suffer premature ejaculation than those given a placebo. Although the Food and Drug Administration rejected J&J’s initial application to sell the drug in 2005, the company continues to explore its options for the novel treatment in the United States and abroad.

Dapoxetine is just one of several drugs that could dramatically reshape the treatment of sexual dysfunction, expanding to more conditions and millions of potential patients, particularly women.

The New Jersey company Palatin Technologies is developing a nasal spray to treat both impotence in men and sexual disorders in women. Procter & Gamble has a testosterone patch for women with low libidos, Intrinsa, that is already sold in Europe. And Boehringer Ingelheim is expecting results from clinical trials next year on flibanserin, an antidepressant that has shown promise as a treatment for women with decreased sexual desire.

There is plenty of room for second-generation “lifestyle drugs.” Although the impotence market seems crowded with Viagra, Cialis and Levitra, a high percentage of patients either don’t respond to the this class of drugs — known as PDE-5 inhibitors — or don’t bother refilling prescriptions. No pill is commercially available for premature ejaculation, which affects more than one in five men.

And most glaring of all, not a single product to treat female sexual dysfunction has been approved yet in the United States.

THE NEXT BIG THING

Those are puzzling gaps for Big Pharma, which is locked in an increasingly desperate search for blockbuster drugs. One reason for the lack of products is a dearth of research, industry observers said. Another is the next generation of sexual dysfunction drugs is more complex than Viagra.

Some of the most promising, such as dapoxetine or the Palatin spray, work through the brain, which raises the regulatory bar for treating conditions that can impair quality of life but are not life-threatening.

Some companies are willing to endure greater regulatory scrutiny because of the perceived size of the market. A 1999 study in the Journal of the American Medical Association found 43 percent of women suffer some form of sexual dysfunction. Critics have challenged the design of the survey and how the results have been interpreted, but that hasn’t stopped biotechs or analysts from building a business model around it.

“The market, we think, is at least as big or bigger in the United States than the market for erectile dysfunction,” Stephen Simes, chief executive of BioSante, told investors at the BIO CEO forum in New York two weeks ago.

BioSante, a biotech in Illinois, is developing a testosterone cream for women called LibiGel, which is in Phase III trials. In some earlier studies, the gel appeared to perform as well or better than the Intrinsa patch, which was approved for sale in Europe last year.

“We at BioSante view this as a very sexy product from all points of view,” Simes said.

The pace of drug development is not the only issue when it comes to treating sexual disorders. Sex therapists cite a host of psychological factors that can impair sexual desire, including stress, depression or domestic abuse. A journalist, Ray Moynihan, helped spark a volatile debate about the definition of female sexual dysfunction four years ago when he suggested in the British Medical Journal that it was essentially a creation of the pharmaceutical industry.

The Moynihan article led to an angry backlash from critics who said it ignored the impact of menopause, changes from childbirth, and surgery or drug side effects on sexual desire and arousal.

“We’re not just talking about yuppies who have gotten to the point where they’re singing the Peggy Lee song, ‘Is That All There Is?’,” said David Ferguson, a pharmaceutical industry consultant and editor of Women’s Sexual Health Journal. “Female sexual dysfunction is very real and is very painful for people who have it.”

Still, there is no single magic therapy to solve those ills. Ten years ago, a pioneering sex researcher at Rutgers University, Beverly Whipple, had to refute the idea her studies could soon lead to an “orgasm pill.” Whipple, co-author of “The Science of Orgasm” and other books about sexual function, said that remains the case.

“We’re searching for the Holy Grail, as if there’s something out there,” she said. “Women are so complex.”

Whipple said she dislikes the term sexual dysfunction because “we don’t know function that well.” Some of her research, done in conjunction with neuroscientist Barry Komisaruk, looked at women with spinal cord injuries. The pair found there was more than one path to the brain to produce an orgasm.

Whipple laments the lack of funding for scientific studies on sexual response. The problem is particularly acute when it comes to women, since most research in the field is geared to men. Pfizer, for example, spent eight years trying to prove Viagra was effective in treating female sexual dysfunction before it gave up.

Viagra did direct more blood to female test subjects’ genitals, just as it did in men, but it did little to increase desire or arousal, Whipple said.

“You can’t take something developed for men and extrapolate the findings,” she said.

TESTING TESTOSTERONE

Some companies are trying that approach with testosterone, however. The hormone appears naturally in both men and women, although in smaller amounts in the latter.

Women who have their ovaries removed can lose up to 50 percent of their testosterone production, which could explain some reduction in sexual desire, Whipple said. But there can be side effects in testosterone therapy for women, including a deepening of the voice or facial hair, she said.

Besides P&G and BioSante, Vivus is looking into a testosterone spray. Officials of the California biotech said they have been in conversations with the FDA for two years, and are still trying to resolve safety concerns.

Ferguson, the pharmaceutical consultant, said he expects a testosterone product will eventually be approved in the United States, but with a label that will limit its use.

“I suspect it will not be a runaway marketing success,” he said.

A likelier breakthrough, he said, is a drug that targets the central nervous system, as Palatin’s product does. Ferguson said he did some initial consulting for the Cranbury biotech.

Because it goes through the brain, the active ingredient in the nose spray, bremelanotide, has a different mechanism of action than other erectile dysfunction drugs, and only takes 15 to 20 minutes to work, according to the company’s chief executive, Carl Spana. A drug application for the male version of the drug could be filed by late 2008, while the female version would come a few years later, Spana said at the BIO CEO forum.

“The big positive for Palatin is it’s an on-demand therapy,” said Ilya Kravets, an analyst for Rodman & Renshaw. “The person takes it, gets the effect they want and then it’s out of their system. Compared to testosterone, this is a big positive for them.”

The same fast-acting, quick-disappearing qualities apply to dapoxetine, which means it doesn’t require a daily dose. J&J hasn’t shared the reason why it was rejected, but Thor — who said he possesses no inside knowledge but has followed the drug’s progress because “it’s one of my children” — said it was probably tied to safety concerns for the class of drugs that dapoxetine belongs to, selective serotonin reuptake inhibitors, or SSRIs.

“My speculation is the timing was just terribly bad,” said Thor, a researcher for Urogenix in North Carolina. “Dapoxetine was submitted just about the same time that all SSRIs took a label about the potential for suicide in depressed patients, in particular young patients.”

A J&J spokeswoman declined to discuss the rejection letter, other than to say: “We have met with the FDA and are continuing to explore our options for dapoxetine in the United States.”

Besides regulatory hurdles, the drugs face uncertainty about affordability. Since the beginning of the year, impotence drugs are no longer covered under Medicare Part D plans, although they are sometimes eligible for reimbursement under supplemental plans.

In 2005, about 30 percent of the employers and health-care plans that worked with Medco Health Solutions, the nation’s biggest pharmacy benefits manager, excluded erectile dysfunction drugs from coverage. Medco’s clients may have become less restrictive in 2006, said Lon Castle, Medco’s director of medical policy.

“It seems to me, over the course of the year, more clients seem to be inclined to cover these drugs,” he said.

It’s difficult to know how female sexual dysfunction drugs will be handled, since there isn’t a lot of data yet, he said. “They probably won’t be handled any differently,” he said.