BioSante’s LibiGel Safety Study Concludes As Additional Efficacy Trials Loom On Horizon
This article was originally published in The Pink Sheet Daily
Executive Summary
Ending the cardiovascular and breast cancer safety study provides significant cost savings and there is sufficient data to show safety prior to approval, CEO Simes says.
BioSante Pharmaceuticals Inc. will garner savings from its decision to end the safety trial for its female sexual dysfunction therapy LibiGel as it faces the expense of two new efficacy studies on the path to an NDA submission for the testosterone gel to treat hypoactive sexual desire disorder in menopausal women.
Ending the safety study “at this time will result in significant on-going cost savings to BioSante,” President and CEO Stephen Simes commented in a Sept. 4 press release announcing the company’s plans.
The savings could help the firm weather a second round of efficacy studies for LibiGel. Greater-than-expected placebo response undercut the statistical significance of LibiGel efficacy in two previous Phase III trials (Also see "BioSante LibiGel Study Design Changes Could Yield Better Results For Sexual Dysfunction" - Pink Sheet, 11 Jun, 2012.).
The company hopes to finalize a Special Protocol Assessment with FDA by the first quarter of 2013. Endpoints for the next set of trials are expected to be the same as in the prior studies – an increase in the number of satisfying sexual events and sexual desire, and decreased distress associated with low desire. One option for altering the study to show a greater difference between LibiGel and placebo patients would be to have patients report outcomes less frequently than the daily diary previously used, with expectations of reducing the placebo effect.
BioSante added about $3.3 million to its bankroll after deducting placement agent and other fees from the sale of $3.475 million in stock and warrants to a single institutional investor in mid-August. A portion of the proceeds will go for LibiGel clinical activities, but also to pay off 3.125% convertible senior notes due May 1, 2013.
The company reported about $42.4 million in cash and cash equivalents on hand as of June 30. Its financial statement showed a net loss in the second quarter of $7.3 million, down from $15 million in the same period of 2011. The decrease is attributed primarily to completion of the initial Phase III trials.
No Safety Issues Raised
BioSante decided to end the cardiovascular and breast cancer safety study following favorable findings by a Data Monitoring Committee’s ninth unblinded review of the trial, which is designed to compare the relative safety of LibiGel to placebo, although the DMC recommended continuation as per the FDA-agreed protocol.
“At this time, we believe we have sufficient safety data to provide reasonable assurance of pre-approval safety, the FDA’s requirement,” Simes explained to “The Pink Sheet.” The data monitoring committee has reviewed the data nine times and “no safety issues have been raised,” he added, noting that the rate of cardiovascular events “has been in a relatively narrow range over the last four years.”
At the time of the review, there were 53 adjudicated cardiovascular events in the trial, with a lower than anticipated event rate of about 0.72%. The study tracked cardiovascular death, myocardial infarction and stroke in women 50 years and older and having at least two CV risk factors, such as hypertension and diabetes.
Twenty-seven breast cancers were reported, with a rate of about 0.37%, in line with the expected rate based on participants’ ages, the company reported.
The study collected more than 7,300 women-years of exposure. The average time in the study was 24.5 months, with more than 3,200 subjects participating for more than one year and more than 1,700 patients enrolled for more than two years.
BioSante launched the study in 2008 with plans to collect 12-month data to support the NDA and to follow participants for an additional four years.
Firm Focused On Data For NDA
Women in the study have an average exposure of 24.5 months, double FDA’s request for 12-month data, Simes noted. ”We feel very comfortable concluding the study. Some women have been in the study for more than four years so there is long-term data,” he pointed out.
“Our objective is to have enough data to submit an NDA and potentially to receive FDA approval. If at that time the FDA asks for longer-term data, we would consider initiating a new safety study post-approval.” Simes said. BioSante is blinded to the data and does not know how many events occurred in the LibiGel or placebo arms.
Sponsors have found hypoactive sexual desire disorder and other female sexual dysfunction indications difficult to attain. Pfizer Inc., Boehringer Ingelheim GMBH and Procter & Gamble Pharmaceuticals Inc. have had drugs fall by the wayside and FDA has yet to approve a product in the space.