The Next Wave Of Sex Drugs

In Wake of Viagra, Pharmaceutical Industry Targets Another Male Malady 

JANE SPENCER & SCOTT HENSLEY / Wall Street Journal 24may2005 

The drug industry has made billions by taking the stigma out of the once-taboo subject of erectile dysfunction. Now, it is targeting an equally delicate problem.

A number of pharmaceutical makers, including Johnson & Johnson, Pfizer and several biotech companies, are testing new drugs to treat the sexual complaint of premature ejaculation. The condition affects 15% to 30% of American men, according to many estimates. That makes it more common than erectile dysfunction, which affects about 10% of men. In the wake of the success of impotence drugs like Viagra, which are now a $2.5 billion-a-year industry world-wide, drug companies hope the emerging treatments could represent the next generation of blockbuster lifestyle drugs.

One of the new drugs, Johnson & Johnson's dapoxetine, has been under review by the Food and Drug Administration for six months and soon could be the first treatment approved for the condition. A major study presented yesterday at the American Urological Association annual meeting in San Antonio showed dapoxetine pills could help men with the dysfunction delay orgasm. Before taking the drug, the men in the study ejaculated less than a minute after starting intercourse, on average; the drug helped them last about two to three minutes longer. The study, which also showed the drug has some unpleasant side effects including nausea, has been submitted to the FDA as part of the final stage of the drug-approval process, known as Phase III.

Even before a drug is approved specifically for the condition, some doctors are quietly prescribing a number of existing drugs. The most common are a class of antidepressants that includes Paxil and Zoloft and has been shown to delay orgasm. Other approaches include prescription topical numbing agents such as lidocaine and a range of unproven over-the-counter products, such as the herb damiana. Researchers are also exploring whether erectile-dysfunction drugs like Viagra can alleviate premature ejaculation.

The move to treat the disorder with drugs is sparking debate about whether drugs are always necessary. A number of past studies have shown that nondrug interventions, such as therapy and behavioral changes, can be 70% to 80% effective. Even the new study on dapoxetine found that men taking a placebo were also able to increase their staying power. Some critics worry that the drug industry may try to cast a range of normal sexual behavior as problematic in an effort to create a market for the new drugs.

But like impotence, premature ejaculation is recognized as a legitimate medical diagnosis, and is listed in the official manual of mental disorders used by the psychiatric community. As with other conditions that were once though to be purely psychological, such as depression, research increasingly suggests the condition has a biological basis. The idea of treating it with a pill emerged only recently. Some see it as just the latest step in the drug industry's growing push to target lifestyle issues.

There is some speculation about whether the drugs could delay orgasm in men with normal sexual function — potentially creating an even larger lifestyle market. Jon Pryor, chairman of the University of Minnesota urology department and the principal investigator on the dapoxetine study, says he believes the drug could potentially delay ejaculation in the general male population, though a potential downside could be an inability to achieve orgasm at all. Johnson & Johnson says it is testing the drug strictly on men diagnosed with premature ejaculation and will market it only to that group if it is approved.

Drug makers face some challenges if they want these new drugs to rival the likes of Pfizer's Viagra, which passed the $1 billion sales mark within a year. A report by Merrill Lynch on Johnson & Johnson's drug pipeline estimated that U.S. sales of dapoxetine in 2008 could range from $350 million to $1.15 billion.

Dapoxetine didn't significantly improve the sex lives of everyone who tried it in the study. Less than 50% of the dapoxetine study participants reported "good" or "very good" satisfaction with sex at the end of the study.

One challenge for drug companies, doctors and patients is defining what constitutes "premature." A recent study in the Journal of Sexual Medicine sponsored in part by Johnson & Johnson attempted to define the problem by giving stopwatches to the wives and girlfriends of 1,587 men, and asking them to measure the period between penetration and ejaculation. Men who considered themselves "normal" averaged 7.3 minutes. Men who considered themselves "premature" averaged 1.8 minutes. But the study also found that anxiety over the issue varied greatly.

"The number of men who want to be treated for PE is far less than the men who report having it," says Ira Sharlip, a urologist and spokesman for the American Urological Association.

Johnson & Johnson is confident there will be a market for the drug. "There's a lot of cynicism out there about if this really is a condition or not," says Usman Azam, the company's vice president of urology drug research and development. But he notes that 10 years ago, people thought the same way about impotence.

Dapoxetine works in a similar manner to SSRI (selective serotonin reuptake inhibitors) antidepressants like Paxil, which regulate levels of the neurotransmitter serotonin in the brain — but it works much faster and can be taken one to three hours before sex. Ongoing research suggests that changes in serotonin metabolism in the central nervous system may be responsible for the timing of ejaculation.

Ironically, SSRI antidepressants are known to have sexual side effects such as damping libido. But the sexual side effects may be less-pronounced in a short-acting pill.

Pfizer is also testing a short-acting SSRI to treat premature ejaculation. The experimental drug had progressed to the early clinical trial stage in 2003, according to a review of research projects the company released that year. A Pfizer spokesman declined to give an update on the project but said the company "is conducting studies." Several smaller companies are also working on pills, including Enhance Biotech of North Carolina.

Some doctors have also been studying whether impotence drugs could help men with premature ejaculation. The results are mixed. While one study suggested sildenafil citrate, the active ingredient in Viagra, can delay ejaculation, a more recent study found the drug did not. (Even with Viagra, men lose their erection after ejaculation.)

The new Johnson & Johnson-funded study on dapoxetine involved 2,614 men age 18-77 in stable, heterosexual relationships. All were diagnosed with premature ejaculation. (That meant they typically ejaculated in under two minutes after sex started and felt considerable distress over the issue.) One group took a 30-milligram dose of the drug, another group took a 60-milligram dose, and a third group took a placebo. Wives and girlfriends timed intercourse with a stopwatch over a 12-week period.

Men taking the highest dose of the drug were able to last for just over three minutes, up from an average of 55 seconds. But they also had the highest rate of side effects: About one in five experienced nausea and 6%-7% experienced headache, diarrhea or dizziness. Side effects were milder at the 30-milligram dose. On that dose, men were able to delay ejaculation to about 2.8 minutes. Men in the placebo group were able to delay ejaculation slightly — to about 1.8 minutes.

Page D1

Drug May Delay Premature Ejaculation

DANIEL J. DeNOON (WebMD) / Fox News 23may2005

A new drug keeps the stopwatch ticking longer for men with premature ejaculation.

The finding comes from a study of more than 2,600 monogamous men testing a new drug, dapoxetine, under development by Johnson & Johnson subsidiary Ortho-McNeil, a WebMD sponsor. One to three hours before sexual intercourse, the men took one of two doses of dapoxetine or a placebo pill.

With their partners, the men used a stopwatch to measure their "intravaginal ejaculatory latency time." This measures the time that elapses between vaginal penetration and ejaculation; fewer than two minutes is considered abnormal or capable of causing distress.

Before treatment, they averaged 54 to 55 seconds. There's some support for the "it's all in the mind" crowd because just taking an inactive placebo pill upped the men's time to 1.75 minutes. But the "it's all in the brain" theory got much better support. Men taking dapoxetine increased their time to 2.78 minutes for low-dose dapoxetine (30 milligrams) and to 3.32 minutes for the higher dose (60 milligrams).

That's a meaningful improvement, says study leader Jon L. Pryor, MD, chairman of urologic surgery at the University of Minnesota.

source: http://www.foxnews.com/story/0,2933,157399,00.html 31may2005

Drug Treats Premature Ejaculation

BBC News (UK) 24may2005

Doctors are hailing a new drug that can prevent premature ejaculation during sexual intercourse.

A meeting of the American Urological Association heard how dapoxetine can lengthen the duration of intercourse by three to four times.

Experts believe up to a third of the male population has problems with premature ejaculation.

However, it will still be some time before the drug is available in pharmacies.

Premature ejaculation

The US drug approval agency the Food and Drug Administration is reviewing an application for dapoxetine, which was developed by Ortho-McNeil Pharmaceutical, an affiliate of Johnson and Johnson.

But a spokesman for Otho-McNeil said the company had not decided whether to make similar applications to European regulators.

Dapoxetine is chemically similar to a family of antidepressants called SSRIs (selective serotonin reuptake inhibitors).

It's one of those hidden conditions that can cause terrible problems in a relationship and a great deal of embarrassment Professor Alan White, chairman of the Men's Health Forum

These types of antidepressants are known to have an impact on ejaculation.

Trials of dapoxetine have included 2,614 men aged 18-77 with premature ejaculation, who maintained monogamous sexual relationships for more than six months.

Each received 30mg or 60mg of dapoxetine or a dummy pill over 12 weeks.

Dapoxetine trebled the duration of intercourse. This beneficial effect occurred after the first dose and increased over the study period.

Lead researcher Dr Jon Pryor, who is a urologist at the University of Minnesota, said: "The impact premature ejaculation can have on men and their partners can be devastating for a relationship and, currently, there are no truly optimal therapies for premature ejaculation."

Professor Alan White, professor of men's health at Leeds Metropolitan University and chairman of the Men's Health Forum, said: "This is certainly a problem that affects many men - as many as one in three or four.

"It's one of those hidden conditions that can cause terrible problems in a relationship and a great deal of embarrassment.

"Men are often reluctant to discuss it with their doctor and if a medication became available, it might make them more willing to go and discuss the problem with their doctor."

He said some cases might be amenable to medical treatment, but emphasised that counselling was also important because psychological factors were often also involved.

"Talking can help. Hopefully this drug will also be able to help some men with this terrible condition."

source: http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/4575015.stm 31may2005

New Drug Treats Premature Ejaculation

ED SUSMAN / Science daily 24may2005

SAN ANTONIO (UPI) — Dapoxetine, a new drug meant to treat premature ejaculation in men, could make a bigger impact on the male sexual health market than Pfizer's impotence blockbuster Viagra.

"Premature ejaculation is the most common male sexual dysfunction," said Dr. Jon Pryor, professor and chairman of the department of urologic surgery at the University of Minnesota's Twin Cities Campus in Minneapolis. "About 20 percent of adult males have premature ejaculation at any one time, and 70 percent of men experience premature ejaculation at some time during their lives."

At the annual meeting of the American Urological Association in San Antonio, Pryor described clinical trials involving 2,614 men and their heterosexual partners who were willing to time their sexual activities with stopwatches in order to conduct the trial with the experimental drug. Dapoxetine is being developed by Ortho Urology, a division of Johnson & Johnson in New Brunswick, N.J.

Pryor said Ortho Urology had filed an application with the Food and Drug Administration for approval of dapoxetine for premature ejaculation. He added approval might occur within a year.

As soon as it receives FDA approval, the potential market for dapoxetine is huge, though doctors said how successful it will be in the marketplace depends on a number of factors.

"A lot will depend on how aggressively the company that makes dapoxetine will use direct-to-consumer advertising for premature ejaculation," said Dr. Jonathan Jarow, professor of urology at The Johns Hopkins University in Baltimore.

He noted that aggressive advertising for the erectile dysfunction drugs Viagra, Levitra and Cialis have created a major market — yet the vast majority of the 30 million Americans with erectile dysfunction have not sought treatment. He said the same problems that make men reluctant to discuss and treat erectile dysfunction could impact sales of treatments for premature ejaculation.

Jarow said other drugs in the same class as dapoxetine are now prescribed by doctors for premature ejaculation and are recognized by the American Urological Association as treatments for the condition, but prescriptions of these medications — called selective serotonin re-uptake inhibitors — are for off-label use and therefore their manufacturers cannot advertise them for that purpose.

Pryor said study participants who took dapoxetine were able to increase their time to ejaculation significantly —from less than one minute to more than three minutes following vaginal penetration. He said normal time to ejaculation during sexual intercourse is about 7 to 9 minutes.

In addition to prolonging time to ejaculation, Pryor said, "Sexual satisfaction was improved by both the men and the partners who each filled out questionnaires regarding the experience with dapoxetine." He noted studies on sexual satisfaction often are performed only on one member of the partnership.

"The results with dapoxetine are compelling," Pryor said. "They demonstrate that, for the first time, a medicine can be taken by men on an on-demand basis and provide significant improvement in their premature ejaculation condition." He also said side effects from the drug were mild and infrequent.

Pryor reported on two identical studies in which premature ejaculating men were assigned either a placebo, a 30-milligram dose of dapoxetine or a 60-milligram dose of dapoxetine. The men took the pills about an hour before sexual activity and their partners were provided with stopwatches. The partners started the watches at the moment of vaginal penetration and stopped the timers upon ejaculation.

Before the trial, the study participants averaged 0.91 minutes before ejaculating during sexual intercourse. After 12 weeks of treatment, the 783 men on placebo averaged about 1.94 minutes before ejaculating, the 798 men on the 30-mg dose of dapoxetine ejaculated after an average of 3.02 minutes, and the 758 men on the 60-mg dose ejaculated after an average of 3.65 minutes. Researchers reviewed the patients' time scores every three weeks.

Pryor said perhaps even more important than the prolonged time to ejaculation were the scores of patients on tests of control of ejaculation and other factors related to satisfaction. Before the trial, he said, only 2 percent to 3 percent of the men said they felt control over ejaculation. After the trial about 25 percent of men on placebo said they controlled ejaculation, 50 percent of those on 30 mg of dapoxetine said they controlled ejaculation, 58 percent of those on 60 mg of dapoxetine said they controlled ejaculation.

At the start of the trial, about 21 percent of men on placebo said they were satisfied with their sexual relationship, after the trial 25 percent of those men said they were satisfied. About 21 percent of men taking the 60 mg dose of dapoxetine expressed satisfaction with their sexual lives before the trial started compared with 57 percent at the end of the trial.

At the start of the trial about 20 percent of the partners of the men on placebo were satisfied with their sexual relationship, and after the trial 25 percent of those women said they were satisfied. About 24 percent of the partners of men taking the 60 mg dose of dapoxetine expressed satisfaction with their sexual lives before the trial started compared with 58 percent of those women at the end of the trial.

When one considers that many couples would not participate in the trial when stopwatches ware mentioned, the couples in the trial had to have been highly motivated, suggested Dr. Gregory Broderick, professor of urology at the Mayo College of Medicine, Rochester, Minn.

"I think that means the participants in the study may have had the worse cases of premature ejaculation," Broderick said Monday. He moderated a press briefing that included the details on dapoxetine. "I would expect the numbers to be better if the drug is approved and is used by people without severe premature ejaculation."

source: http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20050524-18044600-bc-us-premature.xml 31may2005