LibiGel^®

LibiGel^® is a gel formulation of testosterone, designed to be quickly absorbed through the skin after a once-daily application on the upper arm, delivering testosterone to the bloodstream evenly over time and in a non-invasive and painless manner. The topical application of LibiGel has the added advantage of reduced skin reactions compared to other forms of transdermal delivery systems (i.e. patches).

The LibiGel development program has been designed to show that LibiGel can safely improve women's sexual desire and the frequency of satisfying sexual events and decrease personal distress associated with low sexual desire in women with HSDD. BioSante has completed two Phase III LibiGel safety and efficacy trials and is conducting a Phase III cardiovascular event and breast cancer safety study.

Though generally characterized as a male hormone, testosterone also is present in women and its deficiency has been found to decrease libido or sex drive. In addition to increasing sexual desire and activity and decreasing sexual distress, studies have shown that testosterone therapy can increase bone density, raise energy levels and improve mood. The goal of testosterone treatment of women complaining of HSDD is to increase the serum testosterone towards the normal range of premenopausal women in an effort to alleviate the symptoms of this disorder.

Development / Regulatory Status

Phase III Efficacy Results
BioSante has completed two Phase III efficacy trials that were randomized, double-blind, placebo-controlled trials which enrolled 597 and 575 surgically menopausal women, respectively, for six-months of therapy. These trials were conducted according to an FDA-agreed special protocol assessment (SPA) agreement. The co-primary endpoints of both LibiGel efficacy trials were the change in the total number of days with a satisfying sexual event from baseline, and the change in mean sexual desire from baseline. The secondary endpoint for both trials was the change in sexual distress from baseline. Subjects recorded their sexually satisfying events in a validated daily diary, during a baseline period and during the full six months of therapy.

As previously reported in December 2011, LibiGel performed very well in the completed Phase III trials. In fact, LibiGel demonstrated dramatic increases in key endpoints: the number of satisfying sexual events increased approximately 80% from baseline and sexual desire increased approximately 100% from baseline. In addition, there was a 90% decrease in distress associated with the low desire in the trials. While LibiGel performed as well as or even better than previous testosterone studies in HSDD we recognize that LibiGel did not show the required statistical separation from placebo in the two completed Phase III trials.

BioSante is developing a new protocol in order to initiate two new LibiGel Phase III efficacy trials to demonstrate the efficacy of LibiGel. This decision is based on an extensive analysis of previous efficacy data, consultation with key opinion leaders (KOLs) in female sexual dysfunction, testosterone therapy and placebo effects, as well as a meeting with the U.S. Food and Drug Administration (FDA). BioSante also intends to continue the on-going LibiGel Phase III cardiovascular and breast cancer safety study as per protocol. LibiGel (testosterone gel) is in development for the treatment of female sexual dysfunction (FSD), specifically, hypoactive sexual desire disorder (HSDD) in menopausal women.

BioSante intends to provide additional trial design information and timing of trial initiation once finalized. BioSante also intends to apply for an FDA Special Protocol Assessment (SPA) agreement prior to initiating the efficacy trials. Currently, it is expected that the efficacy trials will include the same FDA-required efficacy endpoints as prior Phase III efficacy trials: an increase in the number of satisfying sexual events and sexual desire, and decreased distress associated with low desire.

The critical matter at hand is that the placebo treatment arms performed significantly better than placebo in previously reported Phase III testosterone trials. Therefore, the objective of the new LibiGel Phase III efficacy trials is to minimize the placebo effect in order to unmask the real effects of testosterone and for LibiGel to be statistically better than placebo.

BioSante believes that the placebo effect can be minimized based on another testosterone product´s ability to minimize placebo activity in repeated trials and based on our own experience that has been corroborated by consultations with outside key opinion leaders.

Phase III Safety Study
BioSante has concluded the Phase III LibiGel safety study, a randomized, double-blind, placebo-controlled, multi-center, cardiovascular (CV) events and breast cancer study that has completed enrollment of 3,656 women and has accrued over 7,400 women-years of exposure, to date. The women enrolled have been in the study for an average of 24.5 months each with a range from one year up to four years. The decision to conclude the safety study is based on the level of safety data already produced and the need to conduct two new LibiGel efficacy trials.

The LibiGel safety study has tracked a predefined list of CV events, in agreement with the FDA, including CV death, myocardial infarction and stroke in women 50 years of age or older and suffering from at least two CV risk factors including hypertension and diabetes. The objective of the safety study is to demonstrate the relative safety of testosterone compared to placebo in the number of CV events. The incidence of breast cancer also is being tracked over the course of the study. The study represents the largest data base of the safety of testosterone in women. To date, the study´s independant Data Monitoring Committee (DMC) has conducted nine reviews of unblinded safety data and has not raised any safety issue or concern.