Female Sexual Dysfunction - Testosterone

[Michael Scally MD]

BioSante Pharmaceuticals Reports Positive LibiGel® Safety Data in Phase III Program
http://finance.yahoo.com/news/BioSante-Pharmaceuticals-bw-1911141301.html?x=0&.v=1

LibiGel Phase III Safety Study to Continue Under Current FDA-Agreed Protocol Based On Second Unblinded Data Review by Independent Data Monitoring Committee (DMC)

Press Release Source: BioSante Pharmaceuticals, Inc. On Monday February 22, 2010, 7:55 am EST

LINCOLNSHIRE, Ill.--(BUSINESS WIRE)--BioSante Pharmaceuticals, Inc. (NASDAQ:BPAX - News), today announced additional positive safety data in its ongoing LibiGel Phase III clinical development program. For the second time, unblinded data have been reviewed by the independent DMC of the LibiGel Cardiovascular and Breast Cancer Safety Study. Based on this review, the DMC once again unanimously recommended continuation of the study as described in the FDA-agreed LibiGel safety study protocol, with no modifications.

BioSante reported that the DMC reviewed all unblinded adverse events in the safety study including all “serious adverse events” and all “adverse cardiovascular and breast cancer events” in almost 1,200 women-years of exposure. To date, there have been no deaths, only six adjudicated cardiovascular events and only four breast cancers reported. Therefore, in view of the DMC recommendation, the BioSante LibiGel Phase III development program will continue as planned. BioSante targets mid-2011 for submission to the FDA of a new drug application (NDA).

“Based on this second unblinded positive review by the DMC, we believe that our safety study ultimately will provide the safety data needed for our NDA submission and FDA approval of LibiGel,” said Michael Snabes, M.D., Ph.D., BioSante’s vice president of clinical development. “We have known, based on blinded data, and BioSante remains blinded, that the rates of cardiovascular and breast cancer events in the study continue to be significantly lower than expected in those women enrolled in the safety study, all of whom are at the higher end of cardiovascular risk for the intended population. If there was a negative effect of testosterone, the cardiovascular rates would be higher. This recommendation by the DMC supports our belief that LibiGel will be safe for the treatment of female sexual dysfunction (FSD) in post-menopausal women, our target patient population. This outcome represents another significant positive advance for our LibiGel clinical development program,” Dr. Snabes continued.

“The DMC, which for the second time, reviewed the LibiGel safety data on an unblinded basis, confirms what we have learned from the blinded data, that LibiGel does not pose a safety risk to the women in the study,” said Stephen M. Simes, BioSante’s president and CEO. “A DMC can recommend continuing, changing or stopping a study and their main responsibility is to ensure that subjects recruited to the study are not exposed to unnecessary safety risks. Therefore, the DMC’s recommendation to continue the LibiGel safety study unchanged is the best possible outcome of the DMC’s second unblinded review of all adverse events. This is very good news for BioSante and for women since LibiGel remains the lead pharmaceutical product in the U.S. in active development for the treatment of hypoactive sexual desire disorder (HSDD) in surgically menopausal women. We continue to believe that LibiGel can be the first product approved by the FDA for this common and unmet medical need, also referred to as female sexual dysfunction (FSD).”

The Phase III Cardiovascular and Breast Cancer Safety Study is a randomized, double-blind, placebo-controlled, multi-center, cardiovascular events and breast cancer study that will enroll between 2,400 and 3,100 women, exposed to LibiGel or placebo for 12 months. An NDA can be submitted and reviewed by FDA, possibly leading to approval of LibiGel, at that time. After NDA submission and potential approval of LibiGel, BioSante will continue to follow the women enrolled in the study for an additional four years.

The LibiGel safety study is tracking a predefined list of cardiovascular events, in agreement with the FDA, including cardiovascular death, myocardial infarction and stroke, in women 50 years of age or older and suffering from at least two cardiovascular risk factors including hypertension and diabetes. The objective of the safety study is to show the relative safety of testosterone compared to placebo in the number of cardiovascular events. The incidence of breast cancer also will be tracked over the course of the study.

In addition to the Phase III Cardiovascular and Breast Cancer Safety Study, BioSante is conducting two LibiGel Phase III efficacy trials. The Phase III efficacy trials of LibiGel in the treatment of FSD are double-blind, placebo-controlled trials that will enroll up to approximately 500 surgically menopausal women each for a six-month clinical trial. The efficacy trials are being conducted under an FDA approved SPA (special protocol assessment agreement).

As previously announced by BioSante, treatment with LibiGel in a Phase II clinical trial significantly increased satisfying sexual events in surgically menopausal women suffering from FSD. The Phase II trial results showed LibiGel significantly increased the number of satisfying sexual events by 238 percent versus baseline (p<0.0001); this increase also was significant versus placebo (p<0.05). In this study, the effective dose of LibiGel produced testosterone blood levels within the normal range for pre-menopausal women and had a safety profile similar to that observed in the placebo group. In addition, no serious adverse events and no discontinuations due to adverse events occurred in any subject receiving LibiGel. The Phase II clinical trial was a double-blind, placebo-controlled trial, conducted in the United States, in surgically menopausal women distressed by their low sexual desire and activity.

About BioSante Pharmaceuticals, Inc.

BioSante is a specialty pharmaceutical company focused on developing products for female sexual health, menopause, contraception and male hypogonadism. BioSante’s lead products include LibiGel® (transdermal testosterone gel) in Phase III clinical development by BioSante under a U.S. Food and Drug Administration (FDA) SPA (Special Protocol Assessment) for the treatment of female sexual dysfunction (FSD), and Elestrin™ (estradiol gel) developed through FDA approval by BioSante, indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause, currently marketed in the U.S. Also in development are Bio-T-Gel™, a testosterone gel for male hypogonadism, licensed to Teva Pharmaceuticals (NASDAQ:TEVA - News) and an oral contraceptive in Phase II clinical development using BioSante patented technology. The current market in the U.S. for estrogen and testosterone products is approximately $2.5 billion and for oral contraceptives approximately $3 billion. The company also is developing its calcium phosphate technology (CaP) for aesthetic medicine (BioLook™), as a vaccine adjuvant, including for an H1N1 (swine flu) vaccine, and drug delivery. In addition, BioSante will seek opportunities for its GVAX cancer immunotherapies, 2A/Furin and other technologies. Additional information is available online at: BioSante Pharmaceuticals - Improving health for life.

This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The statements regarding BioSante contained in this news release that are not historical in nature, particularly those that utilize terminology such as “will,” “potential,” “continue,” “could,” “should,” “believe,” “can,” ”intends,” “plans,” “expects” or the negative of these words or other words of similar meaning, or future dates, are forward-looking statements. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Uncertainties and risks may cause BioSante's actual results to be materially different than those expressed in or implied by BioSante's forward-looking statements. For BioSante, particular uncertainties and risks include, among others, the difficulty of developing pharmaceutical products, obtaining regulatory and other approvals and achieving market acceptance; the marketing success of BioSante's licensees or sublicensees; the success of clinical testing; BioSante's need for and ability to obtain additional financing; the effect of general business and economic conditions; and risks arising from BioSante's merger with Cell Genesys. More detailed information on these and additional factors that could affect BioSante's actual results are described in BioSante's filings with the Securities and Exchange Commission, including its registration statement on Form S-4 filed in connection with the merger with Cell Genesys and BioSante's most recent annual report on Form 10-K and subsequent quarterly reports on Form 10-Q. The information set forth in this news release speaks only as of the date hereof, and BioSante undertakes no obligation to update or revise any forward looking statement, whether as a result of new information, future events or otherwise.

Contact:
McKinney/Chicago
Alan Zachary, 312-944-6784 ext. 316
azachary@mckinneychicago.com
McKinney | Chicago

 

[Millard]

Re: LibiGel, gel formulation of testosterone, for female sexual dysfunction

BioSante Pharmaceuticals Reports Positive LibiGel® Safety Data in Phase III Program

Nice - testosterone for women finally gaining acceptance! It is certainly better than the methyltestosterone option

 

[Michael Scally MD]

Sexual Desire

Flibanserin - [ame="http://en.wikipedia.org/wiki/Flibanserin"]Flibanserin - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Flibanserin-structural.svg" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/9/92/Flibanserin-structural.svg/220px-Flibanserin-structural.svg.png"@@AMEPARAM@@commons/thumb/9/92/Flibanserin-structural.svg/220px-Flibanserin-structural.svg.png[/ame]
(code name BIMT-17; proposed trade names Ectris and Girosa) is a drug produced by Boehringer Ingelheim - Home . It is currently being investigated as a drug for women with decreased sexual desire. It is a 5-HT1A receptor full agonist, 5-HT2A receptor antagonist, and D4 receptor very weak partial agonist that had initially been developed as an antidepressant.

As with Viagra, the effects of flibanserin were discovered serendipitously after it was trialled as an antidepressant. Although touted as "Female Viagra" flibanserin does not work like any PDE5 inhibitors. Flibanserin does not play a part in transferring increased amounts of blood to the female genital region as PDE5 inhibitors do to the male genital region. Female HSDD (Hypoactive Sexual Desire Disorder) is not similar to its male counterpart Erectile Dysfunction in the way it is treated. Some have argued that Female Sexual Dysfunction is merely Disease Mongering and a ploy to expand a market for sex drugs for women and to medicalize women's sexuality.


For a list of the clinical trials, go to http://clinicaltrials.gov/ct2/results?term=flibanserin

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Boehringer Ingelheim Announces New Data on Flibanserin in Pre-Menopausal Women with Hypoactive Sexual Desire Disorder

http://finance.yahoo.com/news/Boehringer-Ingelheim-prnews-4174750316.html?x=0&.v=1

›New analyses from pivotal Phase III flibanserin trials presented today

Tuesday May 18, 2010, 6:30 pm

RIDGEFIELD, Conn., May 18 /PRNewswire/ -- Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo. Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. for the treatment of HSDD in pre-menopausal women. HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition.

The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY® and VIOLET®) assessing flibanserin 100mg in pre-menopausal women suffering from HSDD.

"These new data offer a unique perspective on the effects of flibanserin 100mg from the patient's point of view. Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them," said John Thorp, MD, study investigator, Professor of Obstetrics and Gynecology, University of North Carolina Medical School.

These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials. According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events (SSE), compared with placebo.

"HSDD is an under-recognized and often misunderstood condition that can take a toll on women," said Peter Piliero, MD, executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We are committed to advancing flibanserin's development to help understand and find a treatment for women affected by this distressing medical condition."

North American Phase III Trial Results

Patient Perspective Analysis

The pooled analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100mg or placebo for 24 weeks. The women evaluated their overall improvement in "bothersome decreased sexual desire" using the Patient's Global Impression of Improvement (PGI-I), which is a 7-point scale from 1 (very much improved) through 4 (no change) to 7 (very much worse). By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved or minimally improved (p<0.0001).

In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively; p<0.0001), using a single-question Patient Benefit Evaluation (Overall, do you believe that you have experienced a meaningful benefit from the study medication?).

Analysis of Completers

The pooled analysis included 971 (flibanserin 100mg qhs: 450; placebo: 521) pre-menopausal women who completed the 24-week trials. In that analysis, flibanserin 100mg significantly increased the frequency of SSE versus placebo (increase of 2.1 events vs. 0.9 events, respectively; p<0.0001) over the 24-week study period. The analysis also found that, compared with placebo, flibanserin 100mg showed statistically significant improved measures of sexual desire using an electronic daily diary or eDiary (primary endpoint) and on the Female Sexual Function Index (FSFI) desire domain (secondary endpoint). Compared with placebo, flibanserin also showed statistically significant improved sexual functioning (as measured by the FSFI total score), and distress related to low sexual desire (based on the Female Sexual Distress Scale-Revised, FSDS-R, total score), which were secondary endpoints.

The FSFI and FSDS-R desire scores are independently developed and validated tools that provide additional measurement of changes in desire over a four-week recall period. The FSFI is a 19-item self-administered questionnaire composed of six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain). The FSDS-R is a 13-item self-administered questionnaire. The total score ranges from zero to 52, with the higher scores indicating more sexual distress.

Pivotal Trials Safety Data

The most commonly reported adverse events (AEs) with flibanserin 100mg in the pivotal North American trials were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.

About Flibanserin

Flibanserin is an investigational compound being developed by Boehringer Ingelheim for the treatment of HSDD in pre-menopausal women. Pooled data from pivotal Phase III trials demonstrated that flibanserin 100mg increased the number of satisfying sexual events (SSE) and sexual desire while decreasing the distress associated with HSDD. The most commonly reported adverse events (AEs) with flibanserin 100mg were mild to moderate and emerged during the first 14 days of treatment. These AEs reported by more women on flibanserin than on placebo included somnolence (daytime sleepiness), dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. The majority of these AEs resolved with continued treatment. About 15 percent of women on flibanserin 100mg and seven percent of women on placebo discontinued treatment due to AEs.

About Hypoactive Sexual Desire Disorder

Low sexual desire is the most commonly reported female sexual complaint. Approximately one in 10 women report low sexual desire with associated distress, which may be HSDD. HSDD is a form of female sexual dysfunction (FSD) and has been recognized as a medical condition for more than 30 years. As defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), HSDD is the persistent or recurrent lack (or absence) of sexual fantasies or desire for any form of sexual activity causing marked distress or interpersonal difficulty and not better accounted for by another disorder (except another sexual dysfunction), direct physiological effects of a substance (including medications), or a general medical or psychiatric condition. Generalized, acquired HSDD is not limited to certain types of stimulation, situations or partners, and develops only after a period of normal functioning. There is an unmet need for women as there is no FDA-approved treatment for HSDD. It can affect women of all ages and at any stage of life.

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies. The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. In 2009, Boehringer Ingelheim posted net sales of US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development. For more information, please visit http://us.boehringer-ingelheim.com‹

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Panay N, Al-Azzawi F, Bouchard C, et al. Testosterone treatment of HSDD in naturally menopausal women: the ADORE study. Climacteric;13(2):121-31.

OBJECTIVE: To evaluate the efficacy and safety of a transdermal testosterone patch (TTP, 300 microg/day) in naturally menopausal women with hypoactive sexual desire disorder (HSDD).

METHODS: A total of 272 naturally menopausal women, predominantly not using hormone therapy, were randomized in this 6-month, placebo-controlled, double-blind, multicenter study to receive twice weekly either TTP or an identical placebo. Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes (SSE) using the Sexual Activity Log, the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale. Safety was assessed by adverse events, laboratory parameters and hormone levels.

RESULTS: The TTP group demonstrated significant improvements in SSE (p = 0.0089) as well as in sexual desire (p = 0.0007) and reduced personal distress (p = 0.0024) versus placebo at 6 months (intent-to-treat analysis, n = 247). The results were significant for all three endpoints in the subgroup (n = 199) not using hormone therapy. Similar numbers of women treated with placebo and TTP discontinued (n = 39, 27.5% vs. n = 26, 20%), reported adverse events (including application site reactions) (n = 101, 71.1% vs. n = 81, 62.3%) and withdrew due to adverse events (n = 20, 14.1% vs. n = 9, 6.9%). No clinically relevant changes were noted in laboratory parameters. Serum free and total testosterone levels increased from baseline in the TTP group (geometric means 5.65 pg/ml and 67.8 ng/dl, respectively, at week 24) within the physiological range; no changes were seen in estradiol and sex hormone binding globulin levels.

CONCLUSIONS: TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy.

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

FDA Advisory Committee To Consider Approving Pill Designed To Boost Women's Sex Lives.

The Washington Post (5/24, Stein - http://www.newsweek.com/id/238360) reports, "A panel of federal advisers will soon" consider "endorsing the first pill designed to do for women what Viagra [sildenafil] did for men: boost their sex lives." The drug known as "flibanserin," which was developed by Germany's Boehringer Ingelheim, may become "the first prescription medication to tap what some have estimated could be a $2 billion market in the United States alone." But, "even before the FDA's Reproductive Health Drugs Advisory Committee meets June 18 to consider the request, the prospect of the drug's approval has triggered debate over whether the medication, like others in the pipeline, represents a long-sought step toward equity for women's health or the latest example of the pharmaceutical industry fabricating a questionable disorder to sell unnecessary -- and potentially dangerous -- drugs."

The creator of a new documentary on "female sexuality" stumbled upon the issue while researching her film, Newsweek (5/23, Kantrowitz, Wingert - http://www.newsweek.com/id/238360) reported. Liz Canner "was bewildered by the purported disease" that some refer to as "female sexual dysfunction." Noting that Vivus executives told her that "43 percent of women had this disorder," Canner asked, "How could that be true if I had never heard of it before?" After "a cross-country quest that included visits with scientists, experts in erotica, and individual women," Canner "ultimately concluded that the catch-all female sexual dysfunction is essentially a phony disease made up by pharmaceutical companies."

Nevertheless, Scripps Howard News Service (5/23, Bowman - http://seattletimes.nwsource.com/html/health/2011905657_drugs24.html) reported that for women, "medical science seems well on the way to deciding that the chief obstacle to sexual interest, if not performance, is in the brain." Boehringer's drug, flibanserin, "is thought to work by reducing serotonin levels in the brain, essentially reducing signals from areas of the brain that inhibit feeling desire." And, "using several scales, the company reported this week that North American women taking the drug experienced an increase of slightly more than one event per month versus women taking a placebo, and that they felt this change represented a 'meaningful benefit' to them."

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Katrina vanden Heuvel discusses Boehringer Ingelheim's flibanserin, the "so-called pink Viagra." The medication, "which will be considered for official federal endorsement by the FDA's Reproductive Health Drugs Advisory Committee on June 18, is indicated as treatment for female sexual dysfunction." While some say the drug is just an attempt by a pharmaceutical company to over-medicalize a condition to provide a cure for which there is no real disease, such as in a DTC advertising campaign ascribing vague symptoms in men to low testosterone ("low T"), vanden Heuvel asserts that the "flibanserin critique comes down to a delicate judgment call -- that a lack of female sexual satisfaction isn't really a problem." She concludes that "there seems to be a sexual double standard at work here."


For pink Viagra, a double standard
http://www.washingtonpost.com/wp-dyn/content/article/2010/06/08/AR2010060802274.html?hpid=opinionsbox1 (washingtonpost.com)

By Katrina vanden Heuvel
Wednesday, June 9, 2010;

Let's get one thing straight. The discovery and development of flibanserin -- the so-called pink Viagra -- by a German pharmaceutical company is not "disease mongering."

The drug, which will be considered for official federal endorsement by the FDA's Reproductive Health Drugs Advisory Committee on June 18, is indicated as treatment for female sexual dysfunction, or hypoactive sexual desire dysfunction (HSDD), and it is something of an unofficial younger sister to Viagra, which Pfizer first delivered to Americans in 1998.

But Ray Moynihan, a lecturer at the University of Newcastle in Australia and the author of the forthcoming book "Sex, Lies and Pharmaceuticals," thinks the drug's development smacks of disease mongering, telling The Post, "People think they are sick when they are not. People become patients when they don't need to be."

Moynihan has been studying and critiquing disease mongering for nearly 25 years. In 2005 he noted that the United States accounts for half of the international drug market. "That doesn't mean the U.S. takes 50 percent of pills," he told Newsweek. "But it does account for half of total spending on drugs." Yet even such statistics are suggestive, not conclusive. Ultimately, his and others' flibanserin critique comes down to a delicate judgment call -- that a lack of female sexual satisfaction isn't really a problem.

Other critics contend that studying the condition in a traditionally "medical" framework at all is inappropriate, wrongly placing HSDD into a purely urogenital context. Sex therapist and feminist Leonore Tiefer founded theNew View Campaign in 2000 "to challenge the distorted and oversimplified messages about sexuality that the pharmaceutical industry relies on to sell its new drugs." In the New View Manifesto, she writes, "Because there are no magic bullets for the sociocultural, political, psychological, social or relational bases of women's sexual problems, pharmaceutical companies are supporting research and public relations programs focused on fixing the body, especially the genitals." Critics such as Tiefer charge that the invention of pink Viagra created the false notion that a problem as multifaceted as female sexual dysfunction could be cured in an overly simple, chemical way.

Since 1997, when the United States legalized direct-to-consumer advertising for prescription drugs, critics have regularly argued that the pharmaceutical industry manufactures a cure, then invents -- or, in many cases, re-brands -- a disease or disorder that needs that new cure. The result, not surprisingly, can be an "over-medicalization" of conditions that people have for years been content to treat without medicine.

Admittedly, the drug industry doesn't help itself. A particularly ridiculous example of over-medicalization is Solvay Pharmaceuticals' "Is It Low T?" campaign, which demands in its TV spots that men who suffer from a number of vague and fairly common symptoms ("Have you noticed a decrease in your enjoyment of life?") go to a Web site just to determine what, exactly, the corporately branded "Low T" is (testosterone deficiency).

But the assumption that pink Viagra is a scam is reactionary and, at worst, chauvinistic and cruel. Tiefer's assessment notwithstanding, there seems to be a sexual double standard at work here. Contrast the criticism of flibanserin with that leveled at Viagra upon its FDA approval a dozen years ago. In March 1998, press coverage focused far more on the drug's implications for Pfizer's stock price and on the parade of aging baby boomers expected to descend upon the dispensary than on the legitimacy of erectile dysfunction as a medical condition. Not so for Viagra's new analogue, which has been covered with considerably more skepticism.

Yet in a sponsored study flibanserin developer Boehringer Ingelheim reported that premenopausal women aged 18 to 50 who took the drug for a month enjoyed almost two more "satisfying sexual experiences" than they had the previous month; those taking a placebo reported about one more satisfying experience. When the initial results of the study were released last November, critics demanded peer review and pointed to Boehringer Ingelheim's sponsoring of the study as proof that the company was subordinating science to sales. But the study was presented last month at the annual meeting of the American College of Obstetricians and Gynecologists, which may give flibanserin the credibility it needs to pass muster with FDA regulators.

In a way, Tiefer is right. The female libido is complex, and each person has a sui generis relationship with sex. All the more reason not to dismiss blithely those extra two monthly "experiences" -- or the drug that seems to result in them -- as easily as the critics do.

Katrina vanden Heuvel is editor and publisher of the Nation and writes a weekly column for The Post.

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

FDA briefing docs for Flibanserin in female hypoactive sexual desire disorder (for Friday’s advisory panel):
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM215437.pdf

BI’s own presentation:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM215438.pdf

FDA’s proposed questions for the panel:
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM215440.pdf

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Drug for Sexual Desire Disorder Opposed by Panel
F.D.A. Panel Opposes Sexual Desire Drug for Women - NYTimes.com

June 18, 2010
By DUFF WILSON

A federal advisory panel on Friday unanimously voted against recommending approving a drug to treat female sexual desire disorder, but it encouraged the company to continue its research.

That vote by the panel, an adviser to the Food and Drug Administration, followed an F.D.A. staff report earlier this week that also recommended against approval. Such advisory votes do not always influence the F.D.A.’s final decision on a drug, but often they do.

The panel, the Reproductive Health Drugs Advisory Committee, voted against a new drug application by Boehringer Ingelheim, a German pharmaceutical company. Dr. Julia V. Johnson, the panel’s chairwoman, said that the drug’s impact was “not robust enough to justify the risks,” which include dizziness, nausea and fatigue, particularly with long-term daily use.

But Dr. Johnson, head of the department of obstetrics and gynecology at the University of Massachusetts Medical School, encouraged Boehringer to perform more research. The drug, originally intended as an antidepressant, was meant to elevate sexual desire in premenopausal women who are distressed by diminished libidos.

Another panel member, Dr. Kathleen Hoeger, a reproductive endocrinologist with the University of Rochester Medical Center, said that the research was “incredibly important” but that more work was required to improve long-term safety.

The Boehringer drug, flibanserin, affects brain chemicals, like dopamine and serotonin, thought to be involved with sexual drive.

The F.D.A. staff found that it had effectively increased the number of sexually satisfying events reported by more than 1,000 women with depressed libido, increasing those events by a statistically significant 0.8 per month in randomized, placebo-controlled experiments.

But the staff found the drug had not been proved to increase women’s desire — a crucial element of the diagnosis, which involves low or no sexual interest to the point of distress in otherwise healthy people.

The diagnosis, called hypoactive sexual desire disorder, is itself controversial. In the last month Boehringer has mounted a publicity campaign promoting the disorder, in advance of F.D.A. decision-making.

Dr. Anita H. Clayton, a Boehringer consultant and psychiatry professor at the University of Virginia, said the desire disorder affected 6 to 10 percent of premenopausal women, although that estimate was challenged by several speakers at the advisory committee hearing.

Boehringer will continue its research on the drug, a company official said after the vote.

“We are disappointed with the advisory committee’s recommendations and will work with the F.D.A. to address questions raised,” Dr. Christopher Corsico, Boehringer’s United States medical director, said in a statement.

Earlier this week, the company said it was also working in other countries to gain approval for the drug. Lara Crissey, a spokeswoman, wrote in an e-mail message, “We are in discussions with various regulatory agencies worldwide.”

The panel’s 11-to-0 vote was the second time in six years that an F.D.A. advisory panel had unanimously opposed a drug maker’s attempt to treat the female sexual dysfunction. There is no approved drug for the condition.

Various hormonal therapies have been tried.

The F.D.A. rejected a proposed testosterone patch from Procter & Gamble in 2004. That product was approved in Europe in 2006 for use by women who suffered low libido after removal of their uterus and ovaries, after all other forms of sex therapy failed. The product, Intrinsa, has been widely used by women in England who are not surgically menopausal.

BioSante Pharmaceuticals of Illinois plans to seek F.D.A. approval next year for a testosterone product called LibiGel, its spokesman, Alan Zachary, said Friday.

Some doctors already prescribe hormone therapies in so-called off-label uses. Over 4 million testosterone prescriptions were written for women’s sexual dysfunctions in 2009, although it has not been approved by the F.D.A. for that, said Stephen M. Simes, BioSante’s president.

Sheryl A. Kingsberg, a psychologist, Case Western Reserve University medical professor and prominent industry consultant, said widespread off-label use of hormonal drugs indicated a pent-up demand for pharmaceutical help for women.

Professor Kingsberg said Friday that she was disappointed in the F.D.A. advisory vote because Boehringer’s product would have been the first one on the market for younger women with the sexual desire disorder, treating them without hormones.

“I certainly hope Boehringer doesn’t give up,” she said in a phone interview. “Flibanserin showed an awful lot of promise. I’m going to have some very, very disappointed patients if there’s nothing for them.”

But Amy Allina, program director for the National Women’s Health Network, an advocacy group, said: “For some it may turn out that there is a drug that provides effective treatment. But this drug is not it.”

 

[HeadDoc]

Re: Flibanserin & Sexual Desire

it may well be that the problem of FHSDD is as much related to the duration and adequacy of a woman's partner. These have nothing to do with anything that can be put into a pill.

Women's motivations for sex: exploring the diagnos... [J Sex Med. 2010] - PubMed result

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

it may well be that the problem of FHSDD is as much related to the duration and adequacy of a woman's partner. These have nothing to do with anything that can be put into a pill.

Women's motivations for sex: exploring the diagnos... [J Sex Med. 2010] - PubMed result

Sex and the Single Drug
Slipstream - Women’s Libido Pills - Can a Third Route Be the Charm? - NYTimes.com

June 25, 2010
By NATASHA SINGER

THERE’S been a lot of hype lately about an experimental drug to treat sexual disinterest in women, a difficulty formerly known as the “Not tonight, Honey, I have a headache” problem.

It turns out to be a polarizing issue.

In a Viagra-flooded culture, where men have access to little blue pills to quell performance anxiety, isn’t it only fair that women should have a sex-enhancement drug of their own? Or, is a woman’s desire so much more complicated and contextual than a man’s that it cannot be localized to a single anatomical deficiency suitable to pharmaceutical remedy? And, by the way, some women’s health advocates ask, why are we seeking to “fix” women when a lack of desire is often a side effect of another malady: the “men don’t know how to please their partners” disease? (There’s no pill for that.)

Right now, there isn’t a federally approved drug in the United States to treat female libido difficulties. But a novel female desire drug, called flibanserin, now under review by the Food and Drug Administration, has stirred up both proponents and detractors. (My colleague Duff Wilson has written in detail about the debate over the drug.)

Clinical trials sponsored by the drug’s maker, Boehringer Ingelheim, reported that pre-menopausal women on flibanserin experienced a small increase in satisfying sexual activity, compared with women taking a placebo. But a panel of independent medical experts, convened by the F.D.A. to vet the drug, voted that its small effect in heightening libido did not outweigh side effects like dizziness and nausea. Boehringer Ingelheim said in a statement that it was disappointed with the panel’s recommendations and would work with the F.D.A. to address the group’s questions.

In the meantime, the parabola of hype and deflation over the so-called pink Viagra illustrates the challenges that drug makers are likely to face as they expand further into quality-of-life issues like sex from more familiar and saturated chronic-problem categories like high cholesterol.

The market potential for quality-of-life issues seems enormous. A 2005 article in the journal Nature Reviews Drugs Discovery, for example, predicted that revenue for female sexual dysfunctiontreatments in the United States could exceed $4 billion annually “with only 15 percent of patients captured on therapy.”

All of this carries caveats, of course. Regulators and doctors tend to be less tolerant of side effects in quality-of-life drugs than they are in medicines intended to mitigate life-and-death diseases. Some industry critics, meanwhile, contend that in the quest to find new and treatable quality-of-life problems, drug makers are not so much identifying unmet needs as they are stoking existing social anxieties to weld to their medicines.

The hunt for the first medical boost for female desire or arousal offers an interesting case study.

Women naturally experience fluctuating levels of desire over the course of their lives. Lessened libido can be prompted by issues like depression, abuse, bad relationships or stress. In a subset of women, doctors say, sexual disinterest can cause significant personal distress, clinically classified as “hypoactive sexual desire disorder.” The question is whether its antidote is therapy, patience, relationship changes, pharmacology or a combination thereof.

Pharmaceutical companies once hoped that Viagra, or other impotence drugs that men take on an occasional basis to increase blood flow to the penis, would similarly bolster arousal in women.

“That didn’t go anywhere,” says Dr. R. Taylor Segraves, a professor of psychiatry at the School of Medicine at Case Western Reserve University in Cleveland, who specializes in sexual disorders. Unlike men, says Dr. Segraves, who is a consultant and investigator for Boehringer Ingelheim, women with difficulties in desire or arousal rarely complain of physical malfunctions.

“I think it was rather naïve on the part of pharmaceutical companies,” he says, “to think that sexuality in females is the same as in males.”

Next, some drug companies turned to hormones as a potential treatment. But in 2004, when an F.D.A. panel met to consider a testosterone patch to treat libido difficulties in women who had had their ovaries removed, the experts said they were concerned that the product might increase the risk of cancer and heart attacks.

Dr. Segraves says that in the absence of an F.D.A.-approved testosterone patch for female desire, some doctors prescribe male testosterone drugs in low doses for women. “How safe that is, I don’t think we have good long-term data,” he says.

The latest attempt, flibanserin, offers a third way to treat the female libido: brain chemicals. The drug was first developed as an antidepressant. The pills didn’t do much to combat depression, Dr. Segraves says, but Boehringer Ingelheim repurposed the product after women in depression studies reported experiencing increased sexual interest.

In North American studies of the drug in premenopausal women, patients using flibanserin reported an average of nearly one more satisfying sexual event per month — oral sex, say, or intercourse — than women taking a daily sugar pill.

Leonore Tiefer, a psychotherapist in Manhattan who specializes in sexual disorders, jokes that the pill’s apparently meager benefit amounts to an additional “three-quarters of an orgasm” a month.

But for women who previously had no satisfying sex at all, even a small increase might be significant.

The fact that drug makers have taken three different medical routes — the circulatory system, the endocrine system and the nervous system — may indicate that female desire is so complicated that an even more novel approach is required: treatment with multiple therapies.

Or it may indicate that some drug makers are simply trying to tailor a sexual difficulty to mesh well with how some of their drugs operate in the body, says Ray Moynihan, a frequent contributor to BMJ, formerly the British Medical Journal, and co-author of a forthcoming book called “Sex, Lies and Pharmaceuticals.”

“The disease seems designed to fit whatever pharmaceutical solution exists at the time,” says Mr. Moynihan. “If it is a disease.”

BUT the hurdles for a female libido drug may be getting higher.

The next edition of the Diagnostic and Statistical Manual of Mental Disorders, a psychiatry reference book, proposes to do away with the old diagnosis of hypoactive sexual desire disorder. In its stead, a new diagnosis would more narrowly define reduced libido as a lack of sexual interest over at least six months, as well as other criteria — a potential change that could create a higher threshold for prescribing drug therapy.

“I think it should be fairly tough to make that diagnosis because, if we have a drug, people are going to be throwing it around right and left,” says Dr. Nada L. Stotland, a psychiatry professor at Rush Medical College in Chicago. “I think it deserves considerably more investigation.”

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Debate on female sexual dysfunction continues
Debate on female sexual dysfunction continues - latimes.com

The FDA's recent rejection of a so-called female Viagra illustrates the divide between doctors on how to detect and treat low sexual desire in women, or if there is even any need to do so.

By Jessica Pauline Ogilvie, Special to the Los Angeles Times
June 28, 2010

A "little pink pill" to solve women's sexual problems probably won't be hitting drugstore shelves anytime soon. But that doesn't mean discussion of the need for it, or lack thereof, is likely to end.

On June 18, an advisory panel for the Food and Drug Administration recommended against the approval of flibanserin, which had been touted as a female Viagra. The FDA can accept or reject the panel's advice but usually chooses to follow it. In many drug approval proceedings, that would be the end of the matter.

In this case, the highly publicized hearing was preceded by a campaign launched by flibanserin's manufacturer, Boehringer Ingelheim, to educate women about the connection between the brain and desire. The campaign, called "Sex. Brain. Body.," never mentioned flibanserin, but the drug is purported to treat low libido by acting on brain chemicals such as serotonin and dopamine.

Together, the hearing and campaign fueled a long-standing debate over how to define, diagnose and treat low sexual desire in women.

Some medical experts say that low libido, or female sexual dysfunction, is a condition that can and should be treated with medication. Others say that a woman's sexuality is far too complex and is affected by too many other aspects of her life to be reduced to treatment with a pill.

This disagreement has been ongoing despite — or, perhaps, because of — the fact that sexual dysfunction disorders were introduced in 1980 to the Diagnostic and Statistical Manual of Mental Disorders, which is used for diagnostic purposes by medical professionals.

Some people are trying to propose that no medication for female sexual dysfunction should be approved because it's a fabricated condition, said Laura Berman, a sex therapist and author of "The Book of Love."

Berman herself disagrees. "There are real medical factors. Sexual response and sexual factors are in part physiological; you can't ignore that."

Divergent studies

Hypoactive sexual desire disorder, which flibanserin was proposed to treat, is one of seven sexual dysfunction disorders currently listed in the DSM that can affect women. It's defined by a near, or complete, lack of sexual fantasies and little to no desire for sex, and it requires that a woman experience distress over her sexual functioning. Among the other disorders are female sexual arousal disorder, defined by the inability to become and stay sufficiently vaginally lubricated; female orgasmic disorder; and pain during intercourse.

Researchers have attempted for years to find solid numbers reflecting how many women suffer from female sexual dysfunction disorders.

One of the most frequently cited studies analyzed data from a 1992 National Health and Social Life Survey. Published in the Journal of the American Medical Assn. in 1999, the study found that 43% of women surveyed, ages 18 to 59, experienced sexual dysfunction. Of that 43%, 22% cited low desire, 14% had problems with arousal and 7% experienced sexual pain. In this and other studies, women younger than 35 were found to experience more distress over their sexual functioning than their older counterparts.

The findings, while still used by experts, came under some scrutiny when the lead researcher later revealed ties to pharmaceutical company Pfizer.

In other studies looking at the prevalence of female sexual dysfunction, results have been notoriously divergent. Over the years, researchers have estimated that from less than 10% to more than 50% of women ages 20 to 65 and 18 to 49, respectively, have experienced notably or long-lasting low sexual desire, according to a paper published in the Archives of Sexual Behavior in 2009.

The inability to establish a more precise number of women affected comes as little surprise to some medical experts. They say there are inherent difficulties in diagnosing female sexual dysfunction.

Untold causes

To begin with, known causes of low sexual desire in women are nearly innumerable.

In older women, hormonal change from menopause may be the culprit. But in younger women there's rarely an underlying physiological factor at play, says Dr. Bernadith Russell, a fellow at the American Congress of Obstetrics and Gynecologistswww.acog.org/ and the chairman of that group's task force on female sexual dysfunction.

"There are some tests that I would do in premenopausal women," she said, including assessments of thyroid function and screening for diabetes or endocrine disorders, "but that's unlikely to be the cause."

The root of the problem is more likely one of myriad emotional and psychological factors that are known to adversely affect women's libidos, including stress, depression, relationship problems, body image, infertility or a history of sexual abuse.

Women's reactions to sex drive also vary, which throws a wrench in the DSM's criteria that a woman experience distress about her sexual functioning in order to be diagnosed with a disorder Some may feel distress over normal, well-documented fluctuations in sex drive, such as those that follow the birth of a child; and some experience distress over their sexual functioning regardless of their level of desire. Such reactions lead researchers to question how much of what's being called dysfunction is a result of cultural expectations.

Other women feel just fine about having a low libido. The same report that established disparate estimates of women affected by sexual problems also found that of all women surveyed, 7% to 26% reported being distressed by having a low sex drive; that's less, in most cases, than those who reported low desire alone. Factors affecting distress included women's age, age at menopause and overall emotional well-being.

Another barrier to diagnosis is that there is no agreement within the medical community about what typical sexual behavior is for humans, male or female.

"Our understanding of normal sexual function is just evolving," said Russell, "so to make a diagnosis of abnormal sexual functioning, we would have to have normal pinned down pretty well, and we don't right now."

There's also a great deal of deviation from one woman to another. One woman's inactive spell, in other words, is another woman's second honeymoon. "I may have a patient who goes, 'something is really off with me — usually I have sex four-five times a day, and lately I'm just not into it that way,'" Russell said.

Questioning motives

The uncertainties surrounding female sexual dysfunction have led some experts to suggest that pharmaceutical companies are jumping to treat the disorder prematurely and are interested primarily in generating profit.

Leonore Tiefer, clinical psychologist at the New York University medical school, spoke against flibanserin at the FDA hearing. Female hypoactive sexual desire disorder "is all about not having satisfying sexual activity, but that sounds to me more like not having a satisfying marriage, not being able to travel, having too much anxiety, or ignorance," she said. "I don't think the medicalization of sex is helpful for people to have a good sex life."

Other experts in the field of psychology say that pointing the finger at problems in a woman's life is just as damaging.

"It's as irresponsible to say that it is only in her head or relationship as it is for people in the medical community to simplify sexual dysfunction to being just a medical condition," Berman said.

For the time being, women seeking help for a low libido are treated with talk therapy, whether from a sex therapist, couples counselor or individual therapist. They may also be prescribed off-label medication including estrogen or testosterone creams, or antidepressants, although premenopausal women with normal menstrual cycles are rarely, if ever, treated with hormones.

But if a pill becomes available and is approved by the FDA, its popularity could quickly trump any slower-going solutions.

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

Following regulatory feedback Boehringer Ingelheim decides to discontinue flibanserin development
http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/08_october_2010_fliba.html

08 October 2010

Boehringer Ingelheim continues to believe in the value that flibanserin would have for women suffering with HSDD. Company will still complete the two most advanced clinical studies.

Ingelheim (Germany), 08 October, 2010 – Boehringer Ingelheim announced today the decision to discontinue the development of its investigational compound flibanserin for the treatment of Hypoactive Sexual Desire Disorder (HSDD).

The company continues to believe in the value that flibanserin would have for women suffering with HSDD, a significant and recognised medical condition which impacts the lives of many women around the world.

“The decision was not made lightly, considering the advanced stage of development,” said Professor Andreas Barner, Chairman of the Board of Managing Directors and responsible for the Corporate Board Division Pharma Research, Development and Medicine. “We remain convinced of the positive benefit-risk ratio of flibanserin for women suffering with HSDD.”

The response of the authorities and the complexity and extent of further questions that would need to be addressed to potentially obtain registration for flibanserin have impacted the company’s decision to focus on other pipeline projects. The company regularly reviews its pipeline projects and updates its priorities accordingly.

In June 2010, the Reproductive Health Drugs Advisory Committee met in Washington to discuss the new drug application (NDA) for flibanserin as a treatment for HSDD in pre-menopausal women. Members of the Committee advised that additional data would be necessary to further support the efficacy and safety profile of flibanserin. Following the Advisory Committee Meeting in June, the U.S. Food and Drug Administration (FDA) issued its Complete Response Letter to the NDA at the end of August.

Boehringer Ingelheim is proud to have contributed to an increased understanding of HSDD through its significant investment into research, development and educational activities. The company will complete the two most advanced clinical studies to add knowledge for the scientific community and women suffering with HSDD.

“The need for a better understanding of HSDD and its possible treatment continues, and we hope the scientific and medical communities will build on the knowledge that Boehringer Ingelheim’s research has provided to find solutions for women who suffer with this disorder,” said Michael Sand, Director, Clinical Research and Global Strategic Leader of flibanserin, Boehringer Ingelheim.

In view of the broad range of therapeutic areas that the Boehringer Ingelheim pipeline currently comprises, the company will be able to re-allocate resources to other areas, such as stroke prevention, diabetes and oncology.

 

[Michael Scally MD]

Re: Flibanserin & Sexual Desire

I am highly doubtful for this therapy, particularly since there is NO independent confirmation of the study results. Add to this that the study was bought and paid for by the manufacturer.

Test articles and study funding provided by Zestra Laboratories, Inc., now owned by Semprae Laboratories, Inc. Manuscript preparation and statistical analyses partially supported by Semprae Laboratories, Inc.

Ferguson DM, Hosmane B, Heiman JR. Randomized, placebo-controlled, double-blind, parallel design trial of the efficacy and safety of Zestra in women with mixed desire/interest/arousal/orgasm disorders. J Sex Marital Ther 2010;36(1):66-86. https://www.zestra.com/assets/pdfs/journal-of-sex-and-marital-therapy.pdf

Over 256 women, age 21 to 65, with acquired mixed female sexual disorders participated in a 16-week randomized, placebo-controlled, double-blind study of Zestra, a topical botanical preparation. Routine outcome instruments measured efficacy and safety. Zestra was well tolerated. The only significant safety finding was mild-to-moderate genital burning seen only in Zestra-treated subjects (14.6%). Zestra provided significant desire, arousal, and treatment satisfaction benefits for a broadly generalized group of women with sexual difficulties.

 

[Michael Scally MD]

Re: Sexual Desire

Testosterone and Sex: What Women Should Be Talking About
Ricki Pollycove, M.D.: Testosterone and Sex: What Women Should Be Talking About

 

[paulmartin]

Re: Sexual Desire

Good read. It is important is that the issue of low libido in women be discussed. It sure would be nice to have some well researched options.

 

[TZTARZAN2000]

Test for women

okay, what if i give my g/f a weekly dose of test. say like 10 mg. a week. will it raise her estrogen automatically? trying to get her off the stupid .001 cream they are telling her to use. she is 51. any tips please.

thamks

 

[Michael Scally MD]

Re: Test for women

okay, what if i give my g/f a weekly dose of test. say like 10 mg. a week. will it raise her estrogen automatically? trying to get her off the stupid .001 cream they are telling her to use. she is 51. any tips please.

thamks

What is the .001 cream? As far as testosterone for women, BioSante Pharmaceutical - BioSante Pharmaceuticals - Products - LibiGel® - is researching their product Libigel. There are many studies on T use in women. Are menopausal symptoms a problem? What is the treatment goal?

 

[Nemesis RR]

Re: Test for women

10mg a week for a woman (long term) may be to high and lead to hair growth and clit enlargment. If anything start much lower.

 

[TZTARZAN2000]

Re: Test for women

okay, some details. first she is 51 and has had a complete hysterectomy. she says she has a problem getting wet. i did not find this to be a problem as with foreplay and me being a new partner everything seemed to be working fine.

this is a new relationship. 2 weeks new to be exact. after having more sex then she has ever had she thinks she is now having trouble again. like i said the dr. has her on the .001 cream that she is supposed to use daily and rub inside her. i said i would be happy to help.

in talking to a fellow gear head at the gym, he said to just give her the 10 mg. and everything would be okay. i have dated a female bodybuilder who used way more then that so i know what you mean about incresed clit size. hers actually started to look like a penis.

i dont want to screw her up, just trying to help her out. my friend is no dr. but very educated and i didnt go into all the details with him. as a personal friend i dont want to throw her/our business out there. i believe his wife has had the same procedure and i know he told me he gives her 10 mg a week.

so if someone can give me some clues if im on the right track and how much to start her out on i would be happy to learn how to help her.

thanks!