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.
Initial analysis of the data from these trials shows that the trials did not meet the co-primary or secondary endpoints. Although there were no statistical differences in the endpoints, all results were in the appropriate directions. LibiGel is in development for the treatment of female sexual dysfunction (FSD), specifically, hypoactive sexual desire disorder (HSDD) in postmenopausal women, for which there is no FDA-approved product.
Subjects in the first trial, called BLOOM-1, who were treated with LibiGel showed an increase of 1.47 days with a satisfying sexual event compared to baseline, while those receiving placebo gel showed an increase of 1.26 days with a satisfying sexual event compared to baseline. The difference between these increases demonstrated a p value of 0.463. In BLOOM-1 there was an increase in the total number of satisfying sexual events of 3.87 from baseline (an increase of 83 percent) in the LibiGel group and in the placebo group there was an increase of 3.52 satisfying sexual events from baseline (an increase of 65 percent) for a p value of 0.698.
Subjects in BLOOM-2 who were treated with LibiGel showed an increase of 1.0 day with a satisfying sexual event compared to baseline, while those receiving placebo gel showed an increase of 1.28 days with a satisfying sexual event compared to baseline. The difference between these increases demonstrated a p value of 0.214.
Subjects in BLOOM-1 showed an increase in mean sexual desire of 0.03 over placebo, a p value of 0.672, while subjects in BLOOM-2 demonstrated an increase in mean sexual desire of 0.03 compared to placebo, a p value of 0.48. Subjects in both trials demonstrated a decrease in sexual distress when treated with LibiGel (p=0.569 and p=0.26) compared to baseline.
Importantly, and as seen in previous pharmacokinetic data, the LibiGel groups in both trials showed an increase in free testosterone levels compared to baseline and placebo. In BLOOM-1 mean free testosterone at baseline was approximately 1.19 pg/ml and 1.10 pg/ml in the placebo and LibiGel groups, respectively. In month six of the trial, free testosterone levels were approximately 1.35 pg/ml and 4.01 pg/ml in the placebo and LibiGel groups, respectively. In BLOOM-2 mean free testosterone at baseline was approximately 1.06 pg/ml and 1.19 pg/ml in the placebo and LibiGel group, respectively. In month six of the trial, free testosterone levels were approximately 1.09 pg/ml and 3.70 pg/ml in the placebo and LibiGel groups, respectively.
The trials demonstrated that LibiGel was generally well tolerated with a safety profile that appears to be comparable to placebo.
Phase III Safety Study
BioSante continues to conduct 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 5,100 women-years of exposure, to date. The study is designed for a total of five years; however, BioSante could use the safety study data as part of a New Drug Application (NDA) submission after the last subject enrolled has completed 12 months of exposure to LibiGel or placebo.
The LibiGel safety study is tracking 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.
