Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News
Drug development in this arena has proven difficult, but some successes have been reported recently.
While men have had Viagra (sildenafil), Cialis (tadalafil), and Levitra (vardenafil) to address their sexual dysfunction issues for about a decade, finding a solution for women’s woes has been more complicated.
The market for female sexual dysfunction (FSD) drugs is believed larger than the market for male sexual dysfunction treatments (estimates range from $4 billion to $5 billion), since the percentage of women with FSD between ages 18 and 59 (43%, according to studies by Edward Laumann and colleagues between 1999 and 2009) is higher than that for men (34%).
Despite these numbers, no FDA-approved treatments for FSD exist—though several drug developers are closer than ever to changing that equation.
Earlier this month, Palatin Technologies reported that its Phase IIB trial evaluating the efficacy and safety of its drug candidate bremelanotide in premenopausal women diagnosed with FSD met its primary and key secondary endpoints.
Women taking bremelanotide showed statistically significant increases in the number of satisfying sexual events (SSEs), and statistically significant improved measures of overall sexual functioning and distress related to sexual dysfunction, compared with placebo.
“We could not be more excited by the results of this study. We believe they support the advancement of bremelanotide into Phase III studies, and it has potential to be a significant treatment option for female sexual dysfunction patients,” Carl Spana, Ph.D., Palatin’s president and CEO, said during a conference call with analysts held to announce the Phase IIb results.
Scramble to Be First
Palatin is one of several drug developers looking to be the first to win FDA approval for an FSD drug. It would not be the first developer to reach Phase III; Apricus Biosciences, for example, completed a Phase III trial for its Femprox (alprostadil and DDAIP HCl) for female sexual arousal disorder, which relaxes the vulvar and clitoral blood vessels, leading to increased blood flow, then to pelvic engorgement and enhanced secretion activity. However, Apricus isn’t expected to pursue additional work on Femprox until it finds a development partner.
In July, investors raised $20 million for startup Sprout Pharmaceuticals, which hopes to succeed where Boehringer Ingelheim failed by bringing flibanserin through development phases to market. Sprout last year bought rights to flibanserin from BI, which ended its development effort in 2010 after FDA concluded additional safety and efficacy data would be needed, then sent the company a Complete Response letter. Interestingly, flibanserin was originally an anti-depressant before BI tried to reposition it for FSD.
And for years, BioSante has sought to develop LibiGel, a testosterone gel for FSD, only to suffer failures in clinical trials. In December 2011, LibiGel’s Phase III efficacy studies failed to meet co-primary or secondary endpoints or show proof of improvement over placebo, though BioSante said the treatment acted as anticipated. The company’s share price quickly plunged from $15 to $3, though it rose in September when BioSante announced plans to conclude a Phase III safety trial, and develop two new Phase III efficacy trials.
If those trials get under way, they will likely be overseen by BioSante’s successor. BioSante agreed last month to merge with ANI Pharmaceuticals in a deal valued at $94 million and set to close in the first quarter of 2013.
Palatin has also dealt with safety concerns in its development of bremelanotide or BMT, a peptide targeting melanocortin receptor 4 (MCR4), the same receptor targeted by two recently approved anti-obesity drugs, Vivus’ Qsymia, and Belviq, to be made by Arena Pharmaceuticals and distributed by Japan’s Eisai.
BMT was originally an intranasal drug, until a minor increase in blood pressure prompted Palatin to change the method of delivery to subcutaneous. In the Phase IIb study, 327 pre-menopausal women with female sexual arousal disorder (FSAD), hypoactive sexual desire disorder (HSDD), or both showed a 50% increase in SSEs with BMT (from 1.6 to 2.4) versus 12% with placebo (from 1.7 to 1.9) in patients taking either 1.25 mg or 1.75 mg doses.
Among secondary endpoints were improved overall sexual function measured by the Female Sexual Function Index; and reduced distress related to sexual dysfunction, measured by the Female Sexual Distress Scale-DAO.
“Very exciting results. I look forward to hearing how things progress from here,” Edward A. (Ted) Tenthoff, senior research analyst with Piper Jaffray, said on the conference call.
A second analyst also appeared to share Palatin’s enthusiasm for its findings: “Unlike other FSD treatments, this drug really has a component that may address some of the multipronged issues that women have with FSD,” Rahul Jasuja, Ph.D., managing director, biotechnology research with Noble Financial Capital Markets.
Addressing The Life Sciences Report in July, Dr. Jasuja predicted a jump in Palatin’s stock price tied to Phase IIb results panning out: “If the study is positive, this may be one of those micro caps that could unravel for a huge increase in market value.” He noted that last year, Palatin racked up $23 million from investors despite investors appearing warmer toward the FSD drug candidates of other developers.
Doubts over FSD
Given the scramble to develop FSD drugs, it would be hard to believe that FSD isn’t universally considered a disease. Over the past decade, some have argued that FSD was mainly an attempt by Big Biopharma to squeeze billions from women the way it did from men through blockbusters like Pfizer’s Viagra, which reaped $1.981 billion in 2011 sales; Eli Lilly’s Cialis, $1.875 billion; and Bayer’s Levitra $425.222 million.
“It has become clear that drug companies have not simply sponsored the science of this new condition; on occasions they have helped to construct it,” Australian journalist Ray Moynihan wrote in the British Medical Journal in 2010, a theme he and co-author Barbara Mintzes, Ph.D., expanded upon in the book “Sex, Drugs, and Pharmaceuticals: How Drug Companies Plan to profit from Female Sexual Dysfunction.”
Over the past decade, others have advanced the idea: “The ‘Pinking’ of Viagra: Drug Industry Efforts to Create and Repackage Sex Drugs for Women” by Heather Hartley, Ph.D. (1969–2008), published 2006 in the journal Sexualities, contended that in addition to pursuing FSD, the industry also promoted off-label use of men’s sex drugs by women.
Not surprisingly, a clinical investigator on Palatin’s Phase IIb study takes exception to that view.
“While there’s some sort of argument from certain sectors saying it’s sort of the pharmaceutical industry pushing a disease, I can tell you that we know that female sexual disorders are real,” said Sheryl Kingsberg, Ph.D., division chief, OB/GYN Behavioral Medicine, University Hospital Case Medical Center, on Palatin’s conference call.
Dr. Kingsberg noted that the disorders have been included in the Diagnostic and Statistical Manual “legitimately for over 30 years, and I’ve been treating hundreds of women.”
DSM-V combined the former DSM-IV diagnoses of hypoactive sexual desire disorder and female sexual arousal disorder into a single sexual dysfunction category, sexual interest/arousal disorder in women.
“The problem is, that it’s not a one-size-fits-all, and that for many women, while there are psychological causes, for another group of women, and a significant group, there are pharmacologic or biologic underlying causes, for which no amount of psychotherapy is going to fix,” Dr. Kingsberg said.
“Having something that will add to my treatment armamentarium and treatment for the generalists out there is tremendously hopeful. Women have been pleading for research to go on, and sort of at least meet halfway some of the research that has been compelling men to get treatment. This has been tremendously exciting, and the women in my practice are going to be very, very happy that research is moving forward.”
Indeed that research should go forward. Besides coming up with new drugs, one key question that needs addressing is, What percentage of women experience FSD? Speaking last year with WBUR radio in Boston, Jan Leslie Shifren, M.D., director of the Menopause Program at Massachusetts General Hospital, said the percentage of women who experience such difficulties hovers around 12%—enough of a gap from 43% to warrant more scrutiny.
Also deserving more scrutiny is the question raised, but not answered, by Dr. Kingsberg: How much psychology and physiology play into FSD—when do symptoms warrant medication, and when might patients be better served by behavioral solutions to struggling with arousal or orgasm?