Flibanserin
Encyclopedia
Flibanserin is a drug
that was investigated by Boehringer Ingelheim as a novel, non-hormonal treatment for pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD). Development was terminated in October 2010 following a negative report by the U.S. Food and Drug Administration.
HSDD is the most commonly reported female sexual complaint and characterized by a decrease in sexual desire that causes marked personal distress and/or personal difficulties. According to prevalence studies about 1 in 10 women reported low sexual desire with associated distress, which may be HSDD. The neurobiological pathway of female sexual desire involves interactions among multiple neurotransmitters, sex hormones and various psychosocial factors. Sexual desire is modulated in distinct brain areas by a balance between inhibitory and excitatory neurotransmitters, serotonin acting as an inhibitor while dopamine and norepinephrine act as a stimulator of sexual desire.
Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that had initially been investigated as an antidepressant
. Preclinical evidence suggested that flibanserin targets these receptors preferentially in selective brain areas and helps to restore a balance between these inhibitory and excitatory effects.
HSDD has been recognized as a distinct sexual function disorder for more than 30 years.
agonist and 5-HT2A receptor
antagonist, is likely to restore the balance between these neurotransmitter systems.
These data were first presented on November 16, 2009 at the congress of the European Society for Sexual Medicine in Lyon, France. The women receiving Flibanserin reported that the average number of times they had “satisfying sexual events” rose from 2.8 to 4.5 times a month. However, women receiving placebo reported also an increase of “satisfying sexual events” from 2.7 to 3.7 times a month. Evaluation of the overall improvement of their condition and whether the benefit was meaningful to the women, showed a significantly higher rate of a meaningful benefit in the flibanserin-treated patient group versus the placebo group. The onset of the Flibanserin effect was seen from the first timepoint measured after 4 weeks of treatment and maintained throughout the treatment period. The overall incidence of adverse events among women taking flibanserin was low, the majority of adverse events being mild to moderate and resolved during the treatment. The most commonly reported adverse events included dizziness, nausea, fatigue, somnolence and insomnia.
(FDA) unanimously voted against recommending approval of Flibanserin. Earlier in the week, a FDA staff report also recommended non-approval of the drug. While the FDA still might approve Flibanserin, in the past, negative panel votes tended to cause the FDA not to approve.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
that was investigated by Boehringer Ingelheim as a novel, non-hormonal treatment for pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD). Development was terminated in October 2010 following a negative report by the U.S. Food and Drug Administration.
HSDD is the most commonly reported female sexual complaint and characterized by a decrease in sexual desire that causes marked personal distress and/or personal difficulties. According to prevalence studies about 1 in 10 women reported low sexual desire with associated distress, which may be HSDD. The neurobiological pathway of female sexual desire involves interactions among multiple neurotransmitters, sex hormones and various psychosocial factors. Sexual desire is modulated in distinct brain areas by a balance between inhibitory and excitatory neurotransmitters, serotonin acting as an inhibitor while dopamine and norepinephrine act as a stimulator of sexual desire.
Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that had initially been investigated as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
. Preclinical evidence suggested that flibanserin targets these receptors preferentially in selective brain areas and helps to restore a balance between these inhibitory and excitatory effects.
HSDD has been recognized as a distinct sexual function disorder for more than 30 years.
Mechanism of action
The proposed mechanism of action refers back to the Kinsey dual control model. Several sex steroids, neurotransmitters, and hormones have important excitatory or inhibitory effects on the sexual response. Among the neurotransmitters, the excitatory activity is driven by dopamine and norepinephrine, while the inhibitory activity is driven by serotonin. The balance between these systems is relevant for a healthy sexual response. By modulating these neurotransmitters in selective brain areas, flibanserin, a 5-HT1A receptor5-HT1A receptor
The 5-HT1A receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gi/Go and mediates inhibitory neurotransmission...
agonist and 5-HT2A receptor
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
antagonist, is likely to restore the balance between these neurotransmitter systems.
Clinical trials
Several large pivotal Phase III studies with Flibanserin were conducted in the USA, Canada and Europe. They involved more than 5,000 pre-menopausal women with generalized acquired Hypoactive Sexual Desire Disorder (HSDD). The results of the Phase III North American Trials demonstrated that
Although the two North American trials that used the flibanserin 100 mg qhs dose showed a
statistically significant difference between flibanserin and placebo for the endpoint of [satisfying sexual events], they
both failed to demonstrate a statistically significant improvement on the co-primary endpoint of
sexual desire. Therefore, neither study met the agreed-upon criteria for success in establishing the
efficacy of flibanserin for the treatment of [Hypoactive Sexual Desire Disorder].
These data were first presented on November 16, 2009 at the congress of the European Society for Sexual Medicine in Lyon, France. The women receiving Flibanserin reported that the average number of times they had “satisfying sexual events” rose from 2.8 to 4.5 times a month. However, women receiving placebo reported also an increase of “satisfying sexual events” from 2.7 to 3.7 times a month. Evaluation of the overall improvement of their condition and whether the benefit was meaningful to the women, showed a significantly higher rate of a meaningful benefit in the flibanserin-treated patient group versus the placebo group. The onset of the Flibanserin effect was seen from the first timepoint measured after 4 weeks of treatment and maintained throughout the treatment period. The overall incidence of adverse events among women taking flibanserin was low, the majority of adverse events being mild to moderate and resolved during the treatment. The most commonly reported adverse events included dizziness, nausea, fatigue, somnolence and insomnia.
FDA approval
On June 18, 2010, a federal advisory panel to the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) unanimously voted against recommending approval of Flibanserin. Earlier in the week, a FDA staff report also recommended non-approval of the drug. While the FDA still might approve Flibanserin, in the past, negative panel votes tended to cause the FDA not to approve.
Withdrawal
On October 8, 2010, Boehringer Ingelheim announced that it would discontinue its development of flibanserin in light of the FDA advisory panel's recommendation.See also
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