FSDClinical Trials

Doro Shin, MPH, Citeline Analyst, Infectious & Genitourinary Diseases

Sexual dysfunction is defined as a disturbance in or pain during the sexual response and can present in various ways. This problem is more difficult to diagnose and treat in women due to the intricacy of the female sexual response and can consist of various physical and psychological components. Female sexual dysfunction (FSD) has been categorized into four different types of disorders: desire, arousal, orgasmic, and sexual pain. The prevalence of FSD in the USA is 43% among females aged 18-59 years, but pharmaceutical treatment options remain limited. (Source: Medtrack Epidemiology Report, last updated 01/06/2012). No drugs have been approved for treating FSD in the United States, and only one has been approved in the European Union. Hormone replacement therapy may improve sexual function, but this is indicated only for menopausal women and excludes a majority of the population suffering from this disease.

According to Trialtrove, a total of 126 industry sponsored trials have been conducted in FSD, a majority of which are Phase II and/or III trials (98/126). Since 2008, 31 trials have been completed, 16 of which reported positive outcomes. Of these 16 trials, 10 were Phase III studies. Currently, the FSD drug landscape remains limited, with only four ongoing trials and an additional five planned trials (Table 1). Among these nine trials, three compounds have reached phase III development: BioSante’s LibiGel, Apricus’ Femprox, and Forest Laboratories’ Savella.

Table 1: FSD drugs in ongoing and planned trials

Two Phase III efficacy trials of LibiGel for the treatment of hypoactive sexual desire disorder (HSDD) were recently completed. BioSante announced the results in December 2011 and stated that the initial analysis indicated that the trials did not meet the co-primary or secondary endpoints. BioSante asserts that the data did trend in the appropriate direction, but the placebo appeared to work just as well as LibiGel in treating HSDD. The company intends to meet with the U.S. Food and Drug Administration (FDA) in order to determine the best path forward and to make a decision during the second quarter of 2012 regarding the clinical development of LibiGel. In the meantime, the Phase III LibiGel safety study continues and a Phase III study of LibiGel for the treatment of FSD in naturally menopausal women remains planned.

While LibiGel aims to treat HSDD, Femprox addresses Female Sexual Arousal Disorder (FSAD). Apricus Bio completed one 400-patient Phase III study of Femprox in China, which demonstrated that the application of Femprox improved the sexual arousal rate of FSAD women without significant adverse effect except for mild topical stimulation. A US and EU clinical advisory board has been established in order to assist in the design of a confirmatory Phase III trial required by the FDA, and Apricus expects to attain guidance from the FDA on the clinical program for a new drug application (NDA) in the first half of 2012. As such, it is likely that the US Phase III trial of Femprox will remain planned for some time.

Savella, a serotonin norepinephrine reuptake inhibitor used in fibromyalgia treatment, is being evaluated as a treatment for provoked vestibulodynia (PVD), which can result in sexual pain disorder. This phase III trial was initiated in October 2010 and projects that the primary endpoints will be attained later this year, in October 2012. However, the study is still recruiting subjects despite a target enrollment of only 20 patients.

In addition to these three Phase III compounds, Sprout Pharmaceuticals, Inc. recently acquired flibanserin for the treatment of HSDD from Boehringer Ingelheim, which was discontinued in October 2010. The primary endpoint was not met in the initial Phase III studies, however, positive results were reported in subsequent Phase III studies. Due to the conflicting data, the FDA response to Boehringer’s NDA advised that additional data would be necessary to further support the efficacy and safety profile of flibanserin. Now Sprout Pharmaceuticals aims to pick up where Boehringer left off and is restarting the pursuit to commercialize flibanserin as a product to treat HSDD.

Despite ongoing activity and some positive data in late stage clinical development, the path toward an approved treatment for FSD has been as complex and intricate as the disease itself. With slow and steady development within the field of FSD, perhaps one day a treatment will finally be approved and address this unmet medical need for women.