Female sexual dysfunction consists of four recognized disorders: decreased sexual desire, decreased sexual arousal, dyspareunia (painful sexual intercourse) and a persistent difficulty in achieving or inability to achieve orgasm (Female Orgasmic Disorder / "Anorgasmia"). In a survey of over 1700 women aged 18 to 59, 43% acknowledged some form of sexual dysfunction. Looking further into the survey results, the data suggested that 32% of the women lacked interest in sex and 26% could not experience orgasm.(1)
At present, no pharmacologic therapies are approved by the FDA for the treatment of Female Sexual Dysfunction. Some treatments have been used off-label, including compounded testosterone preparations, psychotropic medications and phosphodiesterase (PDE-5) inhibitors, with limited efficacy.
Testosterone is the primary circulating androgen in women and is a naturally occurring steroid secreted by the ovaries and the adrenal glands. Contrary to the sudden drop in estrogen during menopause, serum levels of androgens fall gradually as women age primarily due to a decrease in the production of adrenal androgen precursors. Testosterone plays a role in mood, body composition, bone mineral density and has central and peripheral effects on sexual function. Over the two past decades, over 80 studies have been conducted in women with female sexual dysfunction using exogenous testosterone through the oral, transdermal, sublingual or parental route of administration with or without concomitant estrogen therapy, resulting in an increase in sexual desire, arousal, frequency of satisfactory sexual activity, pleasure and responsiveness.
Tefina™ - Female Orgasmic Disorder
The Corporation’s product candidate Tefina™ is an intranasal, low-dose gel formulation of testosterone. Tefina™ is being developed to offer women experiencing Female Orgasmic Disorder (“FOD”) a “use as required” treatment option. FOD is defined as the persistent or recurrent delay in, or absence of, orgasm following normal sexual excitement phase that causes marked personal distress or interpersonal difficulties. The etiology of FOD is often characterized by whether the dysfunction has been lifelong (primary) or acquired (secondary).
If successfully developed and approved, the “use as required” treatment regimen for Tefina™ is intended to present an attractive safety profile with virtually no androgen-related side effects such as acne, facial and body hair growth or deepening of the voice. Moreover, there is no expected risk of skin-to-skin transfer of testosterone to third parties with the nasal dispenser.
In a Phase I study conducted in 2010, the administration of Tefina™ resulted in an increase in plasma testosterone levels without exceeding the “upper limit of normal” testosterone plasma levels. Tefina™ was also shown to induce physiological and subjective sexual arousal within 30 minutes post-administration. To the knowledge of the Corporation, this is the first known study involving testosterone to ever show an increase in genital responsiveness within 30 minutes post-drug (testosterone) administration.
Results of a Tefina™ Phase II trial were released in February 2012. This Phase II trial in women experiencing FOD was studied in a hospital setting by employing the established Vibrotactile Stimulation (“VTS”) FOD research model. Women experiencing primary or secondary FOD were treated with a single dose of Tefina™ or a placebo and then challenged with a VTS device designed to induce orgasm at different time points post dose. Patient reports, Vaginal Pulse Amplitude (“VPA”) – a physiological measurement of blood flow in the vagina corresponding with engorgement of female genitalia, as well as clinically accepted patient questionnaires, were used to measure the response.
Study analysis concluded that of the 58 women that participated in the study during the VTS treatment phase, four women who were administered Tefina™ self-reported an orgasm during VTS treatment, while an additional eight patients treated with Tefina™ reported sensations indicative of an actual orgasm as part of the post-treatment exit interview. Of the patients in the placebo arm, two patients self-reported an orgasm during the VTS treatment, however one of these two patients is believed to have experienced an orgasm during the screening portion of the study, and should have been excluded from proceeding into the treatment phase. Patients treated with Tefina™ demonstrated a statistically significant improvement in VPA versus placebo, and elevation of sexual arousal, as well as positive trends in terms of elevating sensuality, sexual desire and pleasurable genital sensation.
The Corporation initiated enrolment in May 2012 for a second Tefina™ Phase II being conducted in the United States, Canada and Australia. The Tefina™ Phase II study design has an expected enrollment of 240 women experiencing secondary FOD and will be conducted as an ambulatory trial. As part of this double-blinded placebo-controlled study, patients will administer Tefina™ or placebo at home instead of in a hospital setting. The primary efficacy endpoint of the ambulatory trial will be the increase in the occurrence of orgasms over the treatment period compared against baseline levels.
Trial completion is expected in the first half of 2014, however the Corporation may, in accordance with the study protocol, elect to conduct an interim analysis when approximately 50% of patients have completed the study, which is expected to be reached in late 2013.
1) Lauman et al. Sexual dysfunction in the United States: prevalence and predictors. Journal of the American Medical Association. April 1999.