BioSante Pharmaceuticals, Inc. announced completion of enrolment in its ongoing LibiGel (testosterone gel) phase III cardiovascular and breast cancer safety study. LibiGel is in development for the treatment of Female Sexual Dysfunction (FSD), specifically, Hypoactive Sexual Desire Disorder (HSDD) in menopausal women, for which there is no FDA-approved product.

BioSante has been informed by the LibiGel safety study independent Executive Committee regarding the outcome of the sample size analysis that determines the number of subjects to be enrolled in the LibiGel phase III safety study. The FDA-agreed sample size analysis indicates that enrollment should stop, based on meeting a minimum 90 per cent predictive probability of success of the safety study to show the safety of LibiGel at the primary data analysis. As per the protocol, the safety study will continue for 12 months of therapy from the last subject enrolled before the primary analysis will be conducted by BioSante, which will provide the data for BioSante's New Drug Application (NDA) submission anticipated to be made in 2012. The study will continue for five years.

BioSante reported that the independent Data Monitoring Committee (DMC) reviewed unblinded data in over 3,250 women enrolled and over 3,450 women-years of exposure in its LibiGel phase III cardiovascular and breast cancer safety study including 22 adjudicated cardiovascular (CV) events. To date, the cardiovascular event rate is lower than anticipated at approximately 0.58 percent. There have been nine breast cancers reported; also a lower than anticipated rate of approximately 0.24 percent.

Although enrollment is complete, the phase III LibiGel safety study will continue as per the FDA-agreed protocol, without modification, after the sixth unblinded review of study safety data by the DMC, during which no safety issues were identified to BioSante. BioSante remains blinded as to which events fall into the LibiGel arm or the placebo arm of the study.

“Formal completion of enrollment in the LibiGel safety study is based on the third sample size re-estimation analysis, and the first time that BioSante has been informed that the analysis indicates that enrollment should stop. We are very encouraged that after six reviews of all unblinded safety data, no safety issues have been raised to us by the independent DMC,” stated Michael Snabes, MD, PhD, senior vice president of medical affairs for BioSante. “The LibiGel safety study will continue as per protocol and the DMC will continue to take its periodic unblinded looks at all safety data. BioSante will remain blinded until the primary data analysis which, as per protocol, will occur after the last subject enrolled has been in the study for 12 months of therapy.”

The sample size analysis was conducted, by the DMC's unblinded statistician, based on 3,307 subjects enrolled at the time of the analysis and on 22 adjudicated CV events. Since the analysis, an additional 250 subjects have been enrolled. The sample size analysis requires BioSante to stop enrollment of subjects when there is at least a 90% chance of meeting one or both of the following criteria one year after enrollment is completed: the ratio of the rate of CV events on LibiGel compared to placebo has an upper bound of the 97.2% confidence interval = 2, or the 97.2% confidence interval for the risk difference is = 1% (and less than twice the observed CV events in the LibiGel group vs. placebo group).

Subjects have been enrolled in this study for an average of 12.8 months. More than 1,500 subjects have been enrolled in the study for more than a year and over 700 subjects for more than two years. The periodic reviews by the DMC are based on the DMC's protocol-defined mandate in accordance with FDA Guidance on study oversight. BioSante's objective is to submit the LibiGel NDA by the end of 2012.

“LibiGel remains the only product in the world in phase III clinical development for the treatment of HSDD,” said Stephen M Simes, BioSante's president & CEO. “The ability to stop enrollment as per the sample size analysis that indicates a 90 percent predictive probability of success is very encouraging for the outcome of our LibiGel phase III clinical development programme. With this most recent development, we continue to believe that LibiGel will be the first product approved by the FDA to treat HSDD, also referred to as FSD, in menopausal women.”

The phase III LibiGel safety study is a randomized, double-blind, placebo-controlled, multi-centre, cardiovascular (CV) events and breast cancer study that has enrolled over 3,550 women and has accrued 3,800 women-years of exposure. The 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.

LibiGel is a testosterone gel in phase III clinical development for the treatment of women who suffer from Female Sexual Dysfunction (FSD). The on-going phase III efficacy trials are double-blind, placebo-controlled trials that have enrolled over 500 surgically menopausal women each for a six-month clinical trial. The efficacy trials, which have completed enrollment, 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 FSD 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.

BioSante is a specialty pharmaceutical company focused on developing products for female sexual health and oncology.