BioSante Pharmaceuticals, Inc., a specialty pharmaceutical company focused on developing products for female sexual health and oncology, announced successful completion of its principal LibiGel (testosterone gel) pharmacokinetic (PK) study. The top-line results indicate that LibiGel increases levels of free testosterone, bioavailable testosterone and total testosterone in the serum of post menopausal women to within the normal ranges for younger, pre-menopausal women. LibiGel is in development for the treatment of Female Sexual Dysfunction (FSD), specifically, Hypoactive Sexual Desire Disorder (HSDD) in post menopausal women, for which there is no FDA-approved product.
The LibiGel PK study was conducted as part of the required studies to be submitted in the LibiGel New Drug Application (NDA), which is anticipated by the fourth quarter of 2012. The PK study was conducted in 24 post menopausal subjects for a total of 63 days, in the absence of estrogen therapy, as well as in the same women when treated with a transdermal estradiol patch and subsequently oral estrogen. There were no differences in blood levels of testosterone regardless of the absence or presence of estrogen therapy, whether transdermal or oral.
The data from the PK study showed that testosterone blood levels were similar on days 14, 21, 42 and 63 of the study, indicating that there was no buildup of testosterone blood levels with daily LibiGel treatment. Additionally, free and bioavailable testosterone returned to baseline levels within 36-48 hours after the last dose of LibiGel, indicating effective elimination after dosing is discontinued. The testosterone blood levels produced in this study were very similar to those seen in the BioSante LibiGel phase II efficacy trial reported previously, and they were very similar to blood levels observed in transdermal testosterone patch studies, which also demonstrated efficacy in the treatment of HSDD. Importantly, in the LibiGel PK study, there were no measurable increases in blood levels of the most active estrogen, estradiol, which could have occurred as a result of the conversion of testosterone to estradiol. BioSante plans to present the full PK study results at an upcoming medical meeting.
“Significantly, none of the subjects in the LibiGel PK study had average testosterone concentrations above the normal range for younger, pre-menopausal women, a finding that may be a key component in the safety evaluation of LibiGel by FDA,” noted Michael C Snabes, MD, Ph.D., senior vice president of medical affairs at BioSante. “This finding adds to our confidence that the results of our ongoing, long-term safety study of LibiGel will be favourable.”
LibiGel is a testosterone gel in phase III clinical development for the treatment of women who suffer from FSD, specifically HSDD. The two on-going phase III efficacy trials are double-blind, placebo-controlled trials that have each enrolled over 500 surgically menopausal women for a six-month clinical trial. The efficacy trials, which completed enrollment in the first quarter 2011, are being conducted under an FDA-approved Special Protocol Assessment (SPA) agreement. LibiGel is absorbed quickly through the skin after applying a once-daily, pea-sized topical application on the upper arm that delivers testosterone to the bloodstream evenly over time.
In a phase II trial, LibiGel significantly increased the number of satisfying sexual events in surgically menopausal women suffering from HSDD by 238 percent versus baseline (p<0.0001); this increase also was significant versus placebo (p<0.05). In this study, the effective dose of LibiGel produced testosterone blood levels within the normal range for pre-menopausal women and had a safety profile similar to that observed in the placebo group. In addition, no serious adverse events and no discontinuations due to adverse events occurred in any subject receiving LibiGel. The phase II clinical trial was a double-blind, placebo-controlled trial, conducted in the United States, in surgically menopausal women distressed by their low sexual desire and activity.
In addition, BioSante is conducting a phase III LibiGel safety study, which is a randomized, double-blind, placebo-controlled, multi-centre, cardiovascular (CV) events and breast cancer study that completed enrollment of 3,656 women on June 2, 2011 and has accrued over 4,500 women-years of exposure. The safety study will continue for a total of five years, however, BioSante will use the safety study data as part of an 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 show 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.
Upon completion of the statistical analyses of the safety study and efficacy trials, BioSante intends to submit an NDA to the FDA, requesting approval to market LibiGel for the treatment of HSDD in menopausal women. The NDA submission is targeted for the fourth quarter of 2012.
BioSante is a specialty pharmaceutical company focused on developing products for female sexual health and oncology.