Sprout's First-Ever Female Libido Drug Comes With Boxed Warning and Controversy
Published: Aug 20, 2015
August 19, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Raleigh, N.C.-based Sprout Pharmaceuticals announced yesterday, to extended media coverage, that the U.S. Food and Drug Administration (FDA) had approved Addyi (flibanserin) for what is technically called generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, or low sex drive.
The drug comes with a fair amount of controversy, not only because it addressed a sometimes taboo subject in American culture, women’s libido, but because it has been repeatedly turned down by the FDA. The drug was originally developed by Boehringer Ingelheim and acquired in 2011 by Sprout. In 2010, while Boehringer was testing it, the drug was given a Complete Response Letter from the FDA, which basically states that “a new or generic drug will not be approved in its present form.”
Sprout then resubmitted the New Drug Application (NDA) in February 2013 with data from 14 clinical studies on more than 3,000 patients. Again it was rejected by the FDA. Sprout went back to the drawing board, included data from a Phase I pharmacokinetic study and a Phase I driving study in February 2015. On June 4, 2015, an FDA review panel voted 18 to 6 to recommend approval, which the FDA did on Aug. 18.
“It has been a remarkable journey to get to this breakthrough moment. Today we celebrate what this approval means for all women who have long awaited a medical treatment option for this life impacting condition,” said Cindy Whitehead, Sprout chief executive officer in a statement. “We applaud the FDA for putting the patient voice at the center of the conversation and for focusing on scientific evidence.”
The drug will come with a so-called Boxed Warning due to the seriousness of the side effects and the need for a strict monitoring program. The drug can cause severe low blood pressure, which can lead to passing out, particularly dangerous if driving, but dangerous in general. This particular side effect is made worse when taken with alcohol and some other drugs. The drug can only be prescribed by pharmacies that are certified by Sprout and will require training on counseling patients on the risks and side effects, especially the interaction with alcohol. Additional side effects include dizziness, drowsiness, nausea, fatigue, insomnia and dry mouth.
The FDA indicates that the drug’s mechanism of action is unknown. It appears to affect brain receptors associated with mood.
In addition, there has been some disagreement over the history of the three pivotal Phase III trials, Studies 511.71, 511.75, and 511.147 regarding the effectiveness of the drug. All three trials used two co-primary efficacy endpoints, one to evaluate satisfying sexual events (SSEs) and the other for sexual desire. A key secondary endpoint measured distress related to sexual desire.
All three clinical trials showed a statistically significant improvement using the drug compared to placebo in the number of SSEs and in distress related to sexual desire. “The first two trials did not show a statistically significant improvement over placebo in the co-primary endpoint of sexual desire, which was assessed using a daily electronic diary, but did show a statistically significant improvement over placebo for a secondary endpoint that used FSFI [Female Sexual Function Index] to assess sexual desire. The third trial used FSFI as the pre-specified co-primary endpoint for sexual desire and showed a statistically significant improvement over placebo, consistent with the FSFI findings in the two earlier trials.”
The conclusions were that the drug is effective, but there was some disagreement over whether FSFI was the best way to determine that.
A number of critics, including Susan Wood, a former FDA official currently at George Washington University, and Philip Hanno, a urologist at the University of Pennsylvania ’s school of medicine, have suggested that the FDA was pressured into approving the drug.
“I think the FDA was under a lot of pressure,” Hanno said to NBC News “This ‘Even the Score,’ the group which apparently was supported by the pharmaceutical company among others, was very influential and they certainly had a lot of people at the advisory committee meeting who made comments.”
Even The Score is, according to its website, “A campaign for women’s sexual health equity [that] was created to serve as a voice for American women who believe that it’s time to level the playing field when it comes to the treatment of women’s sexual dysfunction.”
The FDA’s advisory committee report addressed the “Publicity and Claims of Gender Bias,” saying, “The FDA rejects claims of gender bias. The FDA’s regulatory decision for each product is based on an assessment of whether the benefits outweigh the risks, and does not take gender into consideration.”